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1.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612533

RESUMO

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.


Assuntos
Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Neoplasias Colorretais/diagnóstico , Hiperplasia , Carcinogênese , Antígenos Virais de Tumores
2.
Cancer Control ; 31: 10732748241244678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38563112

RESUMO

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.


Assuntos
Infecções por HIV , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Colposcopia , Detecção Precoce de Câncer/métodos , Estudos Transversais , Estudos Retrospectivos , Gana , Papillomaviridae/genética , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Programas de Rastreamento/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia
3.
J Med Virol ; 96(4): e29580, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566572

RESUMO

A persistent infection with human papillomavirus (HPV) can induce precancerous lesions of the cervix that may ultimately develop into cancer. Cervical cancer development has been linked to altered microRNA (miRNA) expression, with miRNAs regulating anchorage-independent growth being particularly important for the progression of precancerous lesions to cancer. In this study, we set out to identify and validate targets of miR-129-5p, a previously identified tumor suppressive miRNA involved in anchorage-independent growth and HPV-induced carcinogenesis. We predicted 26 potential miR-129-5p targets using online databases, followed by KEGG pathway enrichment analysis. RT-qPCR and luciferase assays confirmed that 3'UTR regions of six genes (ACTN1, BMPR2, CAMK4, ELK4, EP300, and GNAQ) were targeted by miR-129-5p. Expressions of ACTN1, CAMK4, and ELK4 were inversely correlated to miR-129-5p expression in HPV-transformed keratinocytes, and their silencing reduced anchorage-independent growth. Concordantly, miR-129-5p overexpression decreased protein levels of ACTN1, BMPR2, CAMK4 and ELK4 in anchorage-independent conditions. Additionally, c-FOS, a downstream target of ELK4, was downregulated upon miR-129-5p overexpression, suggesting regulation through the ELK4/c-FOS axis. ACTN1 and ELK4 expression was also upregulated in high-grade precancerous lesions and cervical cancers, supporting their clinical relevance. In conclusion, we identified six targets of miR-129-5p involved in the regulation of anchorage-independent growth, with ACTN1, BMPR2, ELK4, EP300, and GNAQ representing novel targets for miR-129-5p. For both ACTN1 and ELK4 functional and clinical relevance was confirmed, indicating that miR-129-5p-regulated ACTN1 and ELK4 expression contributes to HPV-induced carcinogenesis.


Assuntos
MicroRNAs , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Carcinogênese/genética , Carcinogênese/patologia , Lesões Pré-Cancerosas/patologia , Proliferação de Células/genética , Proteínas Elk-4 do Domínio ets , Actinina/genética
4.
Cancer Discov ; 14(4): 683-689, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38571435

RESUMO

Research on precancers, as defined as at-risk tissues and early lesions, is of high significance given the effectiveness of early intervention. We discuss the need for risk stratification to prevent overtreatment, an emphasis on the role of genetic and epigenetic aging when considering risk, and the importance of integrating macroenvironmental risk factors with molecules and cells in lesions and at-risk normal tissues for developing effective intervention and health policy strategies.


Assuntos
Lesões Pré-Cancerosas , Humanos , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Fatores de Risco
5.
N Engl J Med ; 390(11): 984-993, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38477986

RESUMO

BACKGROUND: A next-generation multitarget stool DNA test, including assessments of DNA molecular markers and hemoglobin level, was developed to improve the performance of colorectal cancer screening, primarily with regard to specificity. METHODS: In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The primary outcomes were sensitivity of the test for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions). Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. Secondary objectives included the quantification of sensitivity for advanced precancerous lesions and specificity for nonneoplastic findings or negative colonoscopy and comparison of sensitivities for colorectal cancer and advanced precancerous lesions between the multitarget stool DNA test and a commercially available fecal immunochemical test (FIT). RESULTS: Of 20,176 participants, 98 had colorectal cancer, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy. With the next-generation test, sensitivity for colorectal cancer was 93.9% (95% confidence interval [CI], 87.1 to 97.7), and specificity for advanced neoplasia was 90.6% (95% CI, 90.1 to 91.0). Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3 to 45.6), and specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2 to 93.1). With the FIT, sensitivity was 67.3% (95% CI, 57.1 to 76.5) for colorectal cancer and 23.3% (95% CI, 21.5 to 25.2) for advanced precancerous lesions; specificity was 94.8% (95% CI, 94.4 to 95.1) for advanced neoplasia and 95.7% (95% CI, 95.3 to 96.1) for nonneoplastic findings or negative colonoscopy. As compared with FIT, the next-generation test had superior sensitivity for colorectal cancer (P<0.001) and for advanced precancerous lesions (P<0.001) but had lower specificity for advanced neoplasia (P<0.001). No adverse events occurred. CONCLUSIONS: The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. (Funded by Exact Sciences; BLUE-C ClinicalTrials.gov number, NCT04144738.).


Assuntos
Adenoma , Neoplasias Colorretais , DNA , Detecção Precoce de Câncer , Fezes , Imunoquímica , Lesões Pré-Cancerosas , Adulto , Humanos , Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , DNA/análise , Detecção Precoce de Câncer/métodos , Fezes/química , Lesões Pré-Cancerosas/diagnóstico , Estudos Prospectivos , Doenças Assintomáticas , Colonoscopia , Sensibilidade e Especificidade , Testes Imunológicos/métodos , Imunoquímica/métodos
6.
N Engl J Med ; 390(11): 973-983, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38477985

RESUMO

BACKGROUND: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. METHODS: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. RESULTS: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7). CONCLUSIONS: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Detecção Precoce de Câncer , Programas de Rastreamento , Lesões Pré-Cancerosas , Adulto , Humanos , Ácidos Nucleicos Livres/sangue , Colonoscopia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/diagnóstico , Programas de Rastreamento/métodos , Sensibilidade e Especificidade
7.
Sci Rep ; 14(1): 6582, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503902

RESUMO

Although pancreatic precancerous lesions are known to be related to obesity and fatty pancreatic infiltration, the mechanisms remain unclear. We assessed the role of fatty infiltration in the process of pancreatic oncogenesis and obesity. A combined transcriptomic, lipidomic and pathological approach was used to explore neoplastic transformations. Intralobular (ILF) and extralobular (ELF) lipidomic profiles were analyzed to search for lipids associated with pancreatic intraepithelial neoplasia (PanINs) and obesity; the effect of ILF and ELF on acinar tissue and the histopathological aspects of pancreatic parenchyma changes in obese (OB) and non-obese patients. This study showed that the lipid composition of ILF was different from that of ELF. ILF was related to obesity and ELF-specific lipids were correlated to PanINs. Acinar cells were shown to have different phenotypes depending on the presence and proximity to ILF in OB patients. Several lipid metabolic pathways, oxidative stress and inflammatory pathways were upregulated in acinar tissue during ILF infiltration in OB patients. Early acinar transformations, called acinar nodules (AN) were linked to obesity but not ELF or ILF suggesting that they are the first reversible precancerous pancreatic lesions to occur in OB patients. On the other hand, the number of PanINs was higher in OB patients and was positively correlated to ILF and ELF scores as well as to fibrosis. Our study suggests that two types of fat infiltration must be distinguished, ELF and ILF. ILF plays a major role in acinar modifications and the development of precancerous lesions associated with obesity, while ELF may play a role in the progression of PDAC.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Lesões Pré-Cancerosas , Humanos , Pâncreas/metabolismo , Neoplasias Pancreáticas/patologia , Transformação Celular Neoplásica/genética , Carcinoma in Situ/patologia , Lesões Pré-Cancerosas/patologia , Obesidade/complicações , Obesidade/patologia , Lipídeos , Carcinoma Ductal Pancreático/patologia
8.
Zhonghua Gan Zang Bing Za Zhi ; 32(2): 140-147, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38514263

RESUMO

Objective: To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. Methods: 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. Results: The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores (r = 0.73, P < 0.001). Conclusion: In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Lesões Pré-Cancerosas , Humanos , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas , Carcinoma Hepatocelular/diagnóstico , Multiômica , Detecção Precoce de Câncer , Biomarcadores , Biomarcadores Tumorais
9.
Pathol Int ; 74(4): 167-186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38482965

RESUMO

Careful microscopic observation of histopathological specimens, accumulation of large numbers of high-quality tissue specimens, and analysis of molecular pathology in relation to morphological features are considered to yield realistic data on the nature of multistage carcinogenesis. Since the morphological hallmark of cancer is disruption of the normal histological structure maintained through cell-cell adhesiveness and cellular polarity, attempts have been made to investigate abnormalities of the cadherin-catenin cell adhesion system in human cancer cells. It has been shown that the CDH1 tumor suppressor gene encoding E-cadherin is silenced by DNA methylation, suggesting that a "double hit" involving DNA methylation and loss of heterozygosity leads to carcinogenesis. Therefore, in the 1990s, we focused on epigenomic mechanisms, which until then had not received much attention. In chronic hepatitis and liver cirrhosis associated with hepatitis virus infection, DNA methylation abnormalities were found to occur frequently, being one of the earliest indications that such abnormalities are present even in precancerous tissue. Aberrant expression and splicing of DNA methyltransferases, such as DNMT1 and DNMT3B, was found to underlie the mechanism of DNA methylation alterations in various organs. The CpG island methylator phenotype in renal cell carcinoma was identified for the first time, and its therapeutic targets were identified by multilayer omics analysis. Furthermore, the DNA methylation profile of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma was clarified in groundbreaking studies. Since then, we have developed diagnostic markers for carcinogenesis risk in NASH patients and noninvasive diagnostic markers for upper urinary tract cancer, as well as developing a new high-performance liquid chromatography-based diagnostic system for DNA methylation diagnosis. Research on the cancer epigenome has revealed that DNA methylation alterations occur from the precancerous stage as a result of exposure to carcinogenic factors such as inflammation, smoking, and viral infections, and continuously contribute to multistage carcinogenesis through aberrant expression of cancer-related genes and genomic instability. DNA methylation alterations at the precancerous stages are inherited by or strengthened in cancers themselves and determine the clinicopathological aggressiveness of cancers as well as patient outcome. DNA methylation alterations have applications as biomarkers, and are expected to contribute to diagnosis, as well as preventive and preemptive medicine.


Assuntos
Carcinoma Hepatocelular , Neoplasias Renais , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Lesões Pré-Cancerosas , Humanos , Epigenômica , Hepatopatia Gordurosa não Alcoólica/patologia , Patologia Molecular , Carcinoma Hepatocelular/patologia , Metilação de DNA , Carcinogênese/genética , Neoplasias Hepáticas/patologia , Neoplasias Renais/genética , Lesões Pré-Cancerosas/patologia , Ilhas de CpG
10.
J Cancer Res Ther ; 20(1): 311-314, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554339

RESUMO

INTRODUCTION: The category of borderline malignancy or unknown malignant potential was added to the WHO's 2017 classification of thyroid tumours. A new histological variety of papillary tumours and Hurthle cell tumours was given as a separate entity. The classification has also adopted the Turin criteria for histological diagnosis of poorly differentiated cancer (PDC). SETTINGS AND DESIGN: Descriptive study. METHODS AND MATERIAL: From July 2018 to June 2022, 200 thyroid neoplasm patients at a tertiary care facility in western Maharashtra were participated in the prospective research over a period of 4 years. STATISTICAL ANALYSIS USED: The descriptive statistics were used to analyse the collected data. AIM: This study was undertaken to compare the old (2004) and new (2016) WHO classifications and their importance in the treatment of thyroid malignancies. RESULTS: Out of 200 cases, the age range of 31 to 40 years had the greatest number of cases. The ratio of females to males was 5:1. In our study, according to the WHO 2004 classification, malignant tumours comprised 57.5% of the cases, while benign tumours 42.5% of the cases. When tumours were subcategorized, the most frequent benign tumour was follicular adenoma (43.5%) and malignant tumour was papillary thyroid carcinoma (37%). Malignant tumours made up 47.5% of the cases when the tumours were reclassified using the revised WHO 2017 classification, followed by borderline tumours with 27.5% of the cases and benign tumours with 25% of the cases. The most frequent borderline tumour was NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features) (17.5%), the most prevalent malignant tumour was papillary carcinoma (including its variant) (32%), and the most frequent benign tumour was follicular adenoma (27%). CONCLUSION: We concluded that the inclusion of the Boderline Category in the new WHO classification significantly improved thyroid cancer management. WHO 2017 classification prevents under diagnosis (in the case of benign tumors) and over diagnosis (in the case of malignant tumors).


Assuntos
Adenocarcinoma Folicular , Adenoma , Lesões Pré-Cancerosas , Neoplasias da Glândula Tireoide , Adulto , Feminino , Humanos , Masculino , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/patologia , Índia/epidemiologia , Compostos Orgânicos , Estudos Prospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Organização Mundial da Saúde
11.
J Cancer Res Clin Oncol ; 150(3): 152, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517548

RESUMO

INTRODUCTION: Long-term survivors have an increased risk of developing secondary solid malignancies (SSMs) after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) with graft-versus-host disease (GVHD) potentially modulating these risks. METHODS: This retrospective study analyzed the cumulative incidences of SSMs after chemotherapy-based conditioning for allo-HSCT patients with acute myeloid leukemia (n = 266) transplanted at the University Hospital Regensburg between 1999 and 2016. RESULTS: The median follow-up was 11.4 years (Interquartile range, 9.0-14.9). The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 44.4% [95% CI (38.3, 50.2)], while the 5-year cumulative incidence of chronic GVHD (cGVHD, requiring systemic immunosuppression) was 36.9% [95% CI (31.1, 42.6)]. The cumulative incidences of secondary squamous cell carcinomas (SCCs) at 10 and 15 years were 4.2% [95% CI (2.2, 7.2)] and 8.1% [95% CI (4.6, 12.8)], while the cumulative incidences of non-SCCs at 10 and 15 years were 5.4% [95% CI (3.1, 8.7)] and 6.9% [95% CI (4.0, 10.8)]. Antithymocyte globulin (ATG) was associated with reduced incidences of SCCs but not of non-SCCs. Patients with grade II-IV aGVHD had increased rates of SCCs after adjusting with patient age and ATG, while patients with cGVHD showed only a trend for increased rates of SCCs. CONCLUSION: The data indicate that aGVHD and cGVHD affect the rates of secondary SCCs. While the use of ATG is associated with lower incidences of SCCs via reduction of GVHD, there was no association of ATG with non-SCCs.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Lesões Pré-Cancerosas , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Soro Antilinfocitário/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/efeitos adversos
12.
J Craniomaxillofac Surg ; 52(4): 413-419, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38443188

RESUMO

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.


Assuntos
Lesões Pré-Cancerosas , Neoplasias Cutâneas , Camundongos , Animais , Feminino , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Oncogenes , Modelos Teóricos , Receptores ErbB/genética
13.
J Cancer Res Ther ; 20(1): 268-274, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554332

RESUMO

BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.


Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/diagnóstico , Focos de Criptas Aberrantes/patologia , Neoplasias Colorretais/patologia , Colo/patologia , Hiperplasia/patologia , Metilação , Genes Supressores de Tumor , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo/patologia , Mucosa Intestinal/patologia
14.
JAMA Netw Open ; 7(3): e244090, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38551562

RESUMO

Importance: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines. Objective: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit. Design, Setting, and Participants: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023. Exposures: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit. Main Outcomes and Measures: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Results: The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592). Conclusions and Relevance: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.


Assuntos
Iodo , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Ácido Acético , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Triagem , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/patologia , Lesões Pré-Cancerosas/diagnóstico , DNA Viral
17.
Zentralbl Chir ; 149(1): 46-55, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-38442883

RESUMO

Today, endoscopy plays a decisive role not only in the detection of colorectal adenomas and carcinomas, but also in the treatment of precancerous lesions, in particular flat adenomas and early carcinomas. In recent years, endoscopic submucosal dissection (ESD) has become increasingly important alongside classic polypectomy and mucosal resection after saline injection using a snare (EMR). Using ESD the lesion is marked, injected submucosally using viscous substances and the mucosa incised and tunneled with a transparent cap and a fine diathermy knife. Particularly in the case of widespread and high-risk lesions ESD enables a quasi-surgical "en bloc" resection almost regardless of size, with a histological R0 resection rate of far over 90% in specialized centers. ESD enables an excellent histopathological evaluation and has a low recurrence risk of 1-3%. Endoscopic full-thickness resection using a dedicated device (FTRD system) represents another addition to the armamentarium. It can be used for circumscribed submucosal, suspicious or scarred changes up to 2 cm in the middle and upper rectum. Endoscopic intermuscular dissection (EID) enables histopathological analysis of the complete submucosa beyond the mucosa and upper submucosal layer by including the circular inner muscle layer within the resection specimen. It reduces basal R1 situations and offers a new perspective for T1 carcinomas through curative, organ-preserving endoscopic therapy, especially in the case of deep submucosal infiltration alone, without other risk factors for metastases. Indications, the procedure itself and significance of the various techniques for premalignant and early malignant lesions in the rectum are presented.


Assuntos
Adenoma , Carcinoma , Lesões Pré-Cancerosas , Humanos , Reto/cirurgia , Endoscopia , Lesões Pré-Cancerosas/cirurgia , Adenoma/cirurgia
18.
BMC Cancer ; 24(1): 299, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443800

RESUMO

BACKGROUND: CT examination for lung cancer has been carried out for more than 20 years and great achievements have been made in the early detection of lung cancer. However, in the clinical work, a large number of advanced central lung squamous cell carcinoma are still detected through bronchoscopy. Meanwhile, a part of CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions are also accidentally detected through bronchoscopy. METHODS: This study retrospectively collects the medical records of patients in the bronchoscopy room of the Endoscopy Department of Zhejiang Cancer Hospital from January 2014 to December 2018. The inclusion criteria for patients includes: 1.Patient medical records completed, 2.Without history of lung cancer before the diagnosis and first pathological diagnosis of primary lung cancer, 3.Have the lung CT data of the same period, 4.Have the bronchoscopy records and related pathological diagnosis, 5.The patients undergoing radical surgical treatment must have a complete postoperative pathological diagnosis. Finally, a total of 10,851 patients with primary lung cancer are included in the study, including 7175 males and 3676 females, aged 22-98 years. Firstly, 130 patients with CT-occult lesions are extracted and their clinical features are analyzed. Then, 604 cases of single central squamous cell carcinoma and 3569 cases of peripheral adenocarcinoma are extracted and compares in postoperative tumor diameter and lymph node metastasis. RESULTS: 115 cases of CT-occult central lung squamous cell carcinoma and 15 cases of squamous epithelial precancerous lesions are found. In the total lung cancer, the proportion of CT-occult lesions is 130/10,851 (1.20%). Meanwhile, all these patients are middle-aged and elderly men with a history of heavy smoking. There are statistically significant differences in postoperative median tumor diameter (3.65 cm vs.1.70 cm, P < 0.0001) and lymph node metastasis rate (50.99% vs.13.06%, P < 0.0001) between 604 patients with operable single central lung squamous cell carcinoma and 3569 patients with operable peripheral lung adenocarcinoma. Of the 604 patients with squamous cell carcinoma, 96.52% (583/604) are male with a history of heavy smoking and aged 40-82 years with a median age of 64 years. CONCLUSIONS: This study indicates that the current lung CT examination of lung cancer is indeed insufficiency for the early diagnosis of central squamous cell carcinoma and squamous epithelial precancerous lesions. Further bronchoscopy in middle-aged and elderly men with a history of heavy smoking can make up for the lack of routine lung CT examination.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Idoso , Feminino , Pessoa de Meia-Idade , Humanos , Masculino , Metástase Linfática , Estudos Retrospectivos , Detecção Precoce de Câncer , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Lesões Pré-Cancerosas/diagnóstico por imagem , Pulmão
19.
Zhongguo Fei Ai Za Zhi ; 27(2): 118-125, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38453443

RESUMO

BACKGROUND: The pathological types of lung ground glass nodules (GGNs) show great significance to the clinical treatment. This study was aimed to predict pathological types of GGNs based on computed tomography (CT) quantitative parameters. METHODS: 389 GGNs confirmed by postoperative pathology were selected, including 138 cases of precursor glandular lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], 109 cases of microinvasive adenocarcinoma (MIA) and 142 cases of invasive adenocarcinoma (IAC). The morphological characteristics of nodules were evaluated subjectively by radiologist, as well as artificial intelligence (AI). RESULTS: In the subjective CT signs, the maximum diameter of nodule and the frequency of spiculation, lobulation and pleural traction increased from AAH+AIS, MIA to IAC. In the AI quantitative parameters, parameters related to size and CT value, proportion of solid component, energy and entropy increased from AAH+AIS, MIA to IAC. There was no significant difference between AI quantitative parameters and the subjective CT signs for distinguishing the pathological types of GGNs. CONCLUSIONS: AI quantitative parameters were valuable in distinguishing the pathological types of GGNs.


Assuntos
Adenocarcinoma in Situ , Adenocarcinoma , Neoplasias Pulmonares , Lesões Pré-Cancerosas , Humanos , Neoplasias Pulmonares/patologia , Inteligência Artificial , Estudos Retrospectivos , Invasividade Neoplásica , Adenocarcinoma/patologia , Adenocarcinoma in Situ/patologia , Tomografia Computadorizada por Raios X/métodos , Lesões Pré-Cancerosas/patologia , Hiperplasia , Pulmão/diagnóstico por imagem , Pulmão/patologia
20.
Pol Merkur Lekarski ; 52(1): 87-94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38518239

RESUMO

OBJECTIVE: Aim: To identify the medical management determinants of the maxillofacial precancerous and benign diseases malignancy. PATIENTS AND METHODS: Materials and Methods: 150 people with maxillofacial cancer and 100 people with precancerous and benign diseases of the same localization were interviewed. RESULTS: Results: There were revealed: a low percentage of detection during check-up (10.2-15.8%), more than a third of cases (35.8-37.4%) are diagnosed by chance; not all patients undergo histological verification of the diagnosis (25.7% in cancerous and 43.2% in precancerous and benign diseases); not all are under follow up observation (24.7-27.7%). The risk of precancerous and benign diseases malignancy is the highest at 40-59 years of age (OR=4.4; 95% CI: 1.9-10.5), andalso increases with the duration of the disease for more than 5 years (2.2; 1.2-4.10 ), in patients who didn't undergo histological verification (2.2; 1.3-3.8), don't follow doctors' recommendation on visits and treatment (2.4; 1.4-4.1), don't trust doctors and are dissatisfied with medical care (2.1; 1.3-3.6). The risk groups of the maxillofacial oncological, precancerous and benign diseases are men, who are 1.5 times more likely to suffer from them than women and are characterized by lower medical care activity. The risk factors of the maxillofacial precancerous and benign diseases malignancy are low financial (4.6; 1.7-12.4) and territorial (3.3; 1.1-10.3) accessibility of medical care, including dental care (2.8; 1.6-4.8). CONCLUSION: Conclusions: It is necessary to improve the prevention and medical care in order to advance the early detection of maxillofacial cancer, taking into account the established medical management determinants of malignancy.


Assuntos
Lesões Pré-Cancerosas , Masculino , Humanos , Feminino , Fatores de Risco , Lesões Pré-Cancerosas/terapia
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