Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.245
Filtrar
1.
J Int Med Res ; 50(7): 3000605221110697, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35822291

RESUMO

OBJECTIVE: The UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy. METHODS: We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m2. RESULTS: Six of the seven patients tolerated 120 mg/m2 irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed. CONCLUSIONS: mCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Glucuronosiltransferase , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/genética , Polimorfismo Genético
2.
Bull Exp Biol Med ; 173(2): 261-264, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35737160

RESUMO

We performed a comparative quantitative analysis of LINE-1 mRNA levels in extracellular total plasma RNA in patients with colon cancer and practically healthy donors. Quantitative multiplex PCR with reverse transcription was used to assess the level of LINE-1 and 18S rRNA mRNA in extracellular total plasma RNA. The median of LINE-1 mRNA values in colon cancer patients (4.95) was significantly higher than in healthy donors (2.3) (p=0.037). It was shown for the first time that the level of LINE-1 mRNA in total RNA from blood plasma can be determined in the format of a liquid biopsy and serve as a new potential non-invasive marker of colon cancer.


Assuntos
Ácidos Nucleicos Livres , Neoplasias do Colo , Neoplasias Colorretais , Proteínas de Ligação a RNA , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Neoplasias do Colo/sangue , Neoplasias do Colo/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , RNA Mensageiro/sangue , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Phytomedicine ; 103: 154234, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689903

RESUMO

BACKGROUND: The Modified Shenlingbaizhu Decoction (MSD) utilizes various phytomedicines has been applied to treat colorectal cancer (CRC). Colorectal cancer stem cells (CSCs) have proven to be tightly associated with CRC progression and metastasis. The mechanism of MSD's inhibitory effect on CSCs has not been determined. PURPOSE: To figure out how MSD inhibits the pluripotency of CSCs and impedes the EMT program. METHODS: The ingredients of MSD extracts were characterized by high-performance liquid chromatography (HPLC). BALB/c-nu mice were transplanted into EGFP labeled SW480 CRC cells and the tumor weight and volume were recorded before and after various doses of MSD treatment. The concentration of TGF-ß1 was quantified with an Enzyme-linked immunosorbent assay. To delineate the logical relationship between EMT and CSCs regulated by MSD, TGF-ß/Smad inhibitor and activator were adopted in tumor-bearing mice and diverse CRC cell lines. Cancer stem cell markers were analyzed by flow cytometry. In vitro analysis of cell motility and viability were done using CCK-8, wound healing, and invasion assay. Immunohistochemistry (IHC) and western blotting (WB) were used for detecting protein expression. The collected results were statistically analyzed with GraphPad Prism 8.0. RESULTS: MSD treatment significantly reduced the size of colorectal cancer tumors and lowered the serum content of TGF-ß1 in mice. Importantly, MSD markedly reduced the expression of pluripotent factors and depressed CD133+ stem cells in the tumor tissues. The TGF-ß/Smad inhibitor neutralized the EMT signaling and lowered the pluripotency by dephosphorylation of SMAD2/3. Similarly, MSD attenuated the pluripotency by limiting TGF-ß/Smad signaling-induced EMT in vivo. MSD inhibited colorectal cancer cell proliferation, migration, and invasion. CONCLUSIONS: MSD inhibits the growth of colorectal cancer. It dampens the pluripotency of CSCs by repressing the TGF-ß-induced EMT program.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Células-Tronco Neoplásicas , Células-Tronco Pluripotentes , Fator de Crescimento Transformador beta1 , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fitoterapia , Células-Tronco Pluripotentes/efeitos dos fármacos , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/patologia , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/sangue
4.
Bioengineered ; 13(6): 14204-14214, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35754345

RESUMO

Colorectal cancer (CRC) is a common gastrointestinal cancer with high incidence and mortality rates. CRC may be associated with regulation of circulating nucleotides. This study aimed to evaluate the serum levels of nucleotide-metabolizing enzymes (ATPase and AMPase) in patients with CRC and to explore the clinical diagnostic value of these enzymes. The gene set variation analysis (GSVA) score of the ATP-adenosine signature was calculated using tumor samples from The Cancer Genome Atlas (TCGA). ATP-adenosine signaling plays a central role in CRC progression. A total of 135 subjects, including 87 patients with CRC and 48 healthy controls, were included. The serum levels of ATPase and AMPase in the CRC group were significantly higher than those in the control group (P < 0.05). Furthermore, ATP and AMP hydrolysis levels significantly increased in the advanced CRC group (P < 0.05). ATP and AMP hydrolysis was decreased by the ENTPDase inhibitors (POM-1 and ARL67156) and CD73 inhibitor (APCP). The sensitivities of ATPase and AMPase were 95.4% and 75.9%, respectively, which were higher than those of CEA (67.8%) and CA19-9 (72.4%). The specificities of ATPase and AMPase were 69.9% and 73.9%, respectively, which were higher than that of CA19-9 (47.8%). The combination of CEA, ATPase, and AMPase demonstrated high sensitivity (92.0%) and specificity (87.0%). Collectively, ATPase and AMPase activities are upregulated in CRC with considerable diagnostic significance. The combination of CEA, ATPase, and AMPase may provide a novel approach for CRC screening.


Assuntos
Monofosfato de Adenosina , Adenosina Trifosfatases , Trifosfato de Adenosina , Neoplasias Colorretais , Nucleotidases , Monofosfato de Adenosina/sangue , Adenosina Trifosfatases/sangue , Adenosina Trifosfatases/genética , Trifosfato de Adenosina/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Humanos , Nucleotidases/sangue , Nucleotidases/genética
5.
Clin Chim Acta ; 531: 318-324, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35500878

RESUMO

BACKGROUND: Early diagnosis is of great significance for the prognosis of colorectal cancer (CRC) patients. Either serum cystatin S (CST4) or DR-70 has been demonstrated to play an important role on the diagnosis for CRC, however, the diagnostic performances of individual and combined detection of serum CST4 and DR-70 for the patients with CRC at early stage have still not been clarified up to now. METHODS: The performances of CST4 and DR-70 were evaluated by ELISA for the early diagnosis of CRC with 288 retrospective serum samples. A training set comprised of 64 patients with early CRC, 64 patients with colorectal benign lesions (CBL), and 64 healthy controls (HC) was used to develop the predictive model for early CRC. And then, data obtained from an independent validation set was applied to evaluate and validate the predictive model. RESULTS: In the training set, the levels of CST4 and DR-70 in early CRC group were significantly higher than that in CBL group/HC group (P < 0.001); serum CST4 presented the AUC of 0.927 for early CRC patients, with 57.8% sensitivity at 95.3% specificity; serum DR-70 presented the AUC of 0.725 for early CRC patients, with 29.7% sensitivity at 95.3% specificity; combination of serum CST4 and DR-70 presented the AUC of 0.941, with 68.8% sensitivity at 93.8% specificity. Additionally, the combination of serum CST4 and DR-70 showed the AUC of 0.940 for early CRC patients, with 71.9 % sensitivity at 89.1% specificity in the validation set. CONCLUSIONS: Both serum CST4 and DR-70 present the diagnostic value for the patients with early CRC, and the combination of CST4 and DR-70 contributes to the further improvement of the early diagnosis for CRC.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Detecção Precoce de Câncer , Cistatinas Salivares , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Humanos , Prognóstico , Estudos Retrospectivos , Cistatinas Salivares/sangue
6.
J Immunother Cancer ; 10(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35101943

RESUMO

Immune checkpoint inhibitors have shown great promise in treating patients with mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). Although single-agent pembrolizumab has been approved for first-line treatment of dMMR/MSI-H metastatic CRC, combination therapy with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibition (ipilimumab/nivolumab) has reported higher response rates. It is unclear whether patients who progress on PD-1 inhibition will respond to CTLA-4 blockade. Here, we report a case series of three patients with dMMR/MSI-H mCRC, where a durable and ongoing response to nivolumab with ipilimumab was achieved after initial progression with pembrolizumab monotherapy. Blood-based biomarkers such as carcinoembryonic antigen and CA 19-9 were employed to assess treatment response and monitor disease progression along with circulating tumor DNA (ctDNA). Our findings indicate ctDNA's potential to accurately monitor response to therapy and detect disease progression, as validated by standard imaging. This case series demonstrates that CTLA-4 rescue is worthy of additional investigation as a treatment strategy after progression on PD-1 blockade in patients with dMMR/MSI-high mCRC. Our data support the utilization and expansion of clinical studies with combination therapies and using ctDNA kinetics as early dynamic marker for therapy response assessment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , DNA Tumoral Circulante , Neoplasias Colorretais , Ipilimumab/uso terapêutico , Nivolumabe/uso terapêutico , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores
7.
Sci Rep ; 12(1): 2495, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169218

RESUMO

Long non-coding RNAs (LncRNAs) play vital roles in the tumorigenesis of many cancers. Single nucleotide polymorphisms (SNPs) of the lncRNA also play vital roles in tumorigenesis. We explored lncRNA rs944289 and rs7990916 polymorphisms and analyzed the relationship between these lncRNA polymorphisms with the colorectal cancer (CRC) risk in a Chinese population. We recruited 1003 CRC patients from the Affiliated People's Hospital of Jiangsu University and the Fujian Medical University Union Hospital from October 2014 to August 2017. Genomic DNA was extracted using a DNA Kit from lymphocytes of peripheral blood and the genotyping was performed with a SNPscan method. We found that the rs944289 TT homozygote was associated with the decreased CRC risk in the overall population. LncRNA rs944289 TT decreased the CRC risk in the subgroup of female, male, age ≥ 61, without alcohol intake, smoking and BMI ≥ 24 by logistic regression. The subgroup analysis revealed that lncRNA rs7990916 was not associated with CRC risk except for age < 61. Logistic regression analysis revealed that lncRNA rs944289 TT homozygote was associated with the increased risk of rectum cancer (TT vs. CC + CT: adjusted OR = 1.29, 95% CI 1.10-1.66, P = 0.041) or colon cancer. In summary, we proved that lncRNA rs944289 might be significantly related to the decreased CRC risk in the Chinese Han populations and lncRNA rs7990916 was not associated with the CRC risk except for patients of age < 61. In the future, studies with larger samples should be conducted to validate our results.


Assuntos
/genética , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinogênese/genética , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Colorretais/sangue , Feminino , Predisposição Genética para Doença/genética , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversos
8.
J Mater Chem B ; 10(3): 450-455, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34981801

RESUMO

The simple and sensitive detection of protein is of great significance in biological research and medical diagnosis. However, the commonly-used methods, such as enzyme-linked immunosorbent assay (ELISA), usually rely on signal tags labeled on the antibody, which limits the sensitivity and stability. Herein, we have designed and constructed a colorimetric immunosensor in this work for the analysis of protein by taking advantage of 2D metal-organic framework (2D-MOF) nanomaterials as enzyme mimics. The nanomaterial shows a strong peroxidase mimetic activity, and good selectivity after it is modified with a specific aptamer. Therefore, taking carcinoembryonic antigen (CEA) as an example, this immunosensor achieves a good detection performance with a linear range from 1 pg mL-1 to 1000 ng mL-1 and a limit of detection (LOD) of 0.742 pg mL-1. Moreover, the sensor can successfully distinguish the human serum of colorectal cancer patients from healthy people, which suggests that this sensor has great potential in clinical applications. More importantly, the mass production, low cost, stability and ease of transport of the MOFs nanomaterials, as well as the ability for visual detection will make this sensor suitable for point-of-care (POC) testing in remote or resource-poor areas.


Assuntos
Antígeno Carcinoembrionário/sangue , Colorimetria/métodos , Imunoensaio/métodos , Estruturas Metalorgânicas/química , Nanoestruturas/química , Anticorpos Imobilizados/imunologia , Aptâmeros de Nucleotídeos/química , Benzidinas/química , Biomarcadores/sangue , Antígeno Carcinoembrionário/imunologia , Catálise , Compostos Cromogênicos/química , Neoplasias Colorretais/sangue , Humanos , Ácidos Nucleicos Imobilizados/química , Limite de Detecção
9.
Gastroenterology ; 162(3): 952-956, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35094786

RESUMO

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update Commentary is to review the available evidence and provide expert advice regarding the approach to using noninvasive colorectal cancer (CRC) screening options, including evidence for their effectiveness, selection of individuals for whom these tests are appropriate, implications of a positive non-colonoscopy screening test, and opportunities to enhance the quality of noninvasive CRC screening programs. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary reflects recently published studies in this field, as well as the experiences of the authors who are gastroenterologists with high-level expertise in CRC screening and prevention.


Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , DNA/análise , Detecção Precoce de Câncer/métodos , Sangue Oculto , Adenoma/sangue , Adenoma/urina , Neoplasias Colorretais/sangue , Neoplasias Colorretais/urina , DNA/sangue , Metilação de DNA , Fezes/química , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Medição de Risco , Septinas/genética
11.
Asian Pac J Cancer Prev ; 23(1): 339-348, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35092403

RESUMO

OBJECTIVE: Assessing plasma Cell Free DNA (cfDNA) integrity index as a biomarker for response prediction and early response evaluation in mCRC patients receiving chemotherapy, in comparison to Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9), to be used as an additional tool to computed tomography (CT). METHODS: CEA, CA19-9, cfDNA concentration and cfDNA integrity index (ALU 247/115) measurements were conducted on 86 subjects divided into 43 healthy volunteers and 43 mCRC patients, before starting chemotherapy and then after 6-12 weeks of therapy initiation (3-4 cycles FOLFOX) at first response assessment. Plasma cfDNA integrity index was calculated as the ratio of long to short DNA fragments (ALU 247/115) amplified and detected by real-time PCR. Serum CEA and CA19-9 were measured by chemiluminescent immunometric assay. RESULTS: Baseline cfDNA integrity index was statistically significantly different between responders and non-responders (p=0.03). It was found that at cut off 0.608, sensitivity was 73.7%, specificity was 66.7% and diagnostic accuracy=69.77%. Markers with statistical significant difference between responders and non-responders after chemotherapy were CEA % change (p=0.035), CA19-9 (p=0.024), cfDNA integrity index (p=0.035) and cfDNA integrity index % change (p<0.001). Among these markers, cfDNA integrity index % change had the best sensitivity (84.2%), specificity (95.2%) and diagnostic accuracy (90.7%) at cut off -17.827%. CONCLUSION: Baseline cfDNA integrity index can be used as a potential marker to predict response to chemotherapy. cfDNA integrity index (ALU 247/115) % change rather than its absolute value is superior to CEA, CA19-9, cfDNA concentration and their % changes in early assessment of response to chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Nucleicos Livres/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
13.
Oncology ; 100(1): 22-30, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34794144

RESUMO

OBJECTIVES: Colorectal cancer is the third most common cancer worldwide, with an obvious need for more accurate prognostics. Previous studies identified C-reactive protein (CRP) as a prognostic serum biomarker for colorectal cancer, whereas the biomarkers tumor-associated trypsin inhibitor (TATI) and tumor-associated trypsin-2 (TAT-2) are less well-known prognostic factors. Therefore, in this study, we aimed to compare the prognostic role of these biomarkers. MATERIALS AND METHODS: Our cohort consisted of 219 women and 274 men who underwent colorectal cancer surgery at Helsinki University Central Hospital from 1998 through 2005. Serum and plasma samples were collected before surgery, aliquoted, stored at -80°C, and then analyzed using high-sensitivity methods with commercially available time-resolved immunofluorometric assay kits. RESULTS: In univariate analysis, CRP (HR 1.67; 95% confidence interval [CI]: 1.25-2.23; p = 0.001), TATI (HR 1.87; 95% CI: 1.13-3.08; p = 0.014), and TAT-2 (HR 1.52; 95% CI: 1.13-2.06; p = 0.006) were significant prognostic biomarkers across the entire cohort. In subgroup analyses, TATI and TAT-2 represented significant negative prognostic factors among patients older than 66, while patients with left-sided disease, a high serum TAT-2, or a high plasma CRP experienced worse prognosis. None of the biomarkers emerged as important in the disease stage subgroup analysis nor did they serve as independent factors in the multivariate analysis. CONCLUSIONS: TATI and TAT-2 as well as CRP significantly, but not independently, served as prognostic factors in our cohort of colorectal cancer patients. Further research is needed to fully understand their clinical role in colorectal cancer.


Assuntos
Proteína C-Reativa/análise , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Inibidor da Tripsina Pancreática de Kazal/sangue , Tripsina/sangue , Tripsinogênio/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico
14.
J Clin Lab Anal ; 36(1): e24128, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34811805

RESUMO

BACKGROUND: The focus of this study was to analyze the prognostic value of different combinations of inflammatory and coagulation factors using preoperative blood and to appraise the clinical importance of these biomarkers in colorectal cancer patients. METHODS: A prospective, multicenter study included patients undergoing radical colorectal surgery in three county hospitals. Inflammatory and coagulation markers were analyzed preoperatively. RESULTS: Two hundred and one patients were included. We examined patients based on their tumor localization. Colon cancer group involved patients with the tumor localized in the colon (n = 105, 52.24%) and rectal cancer group the patients with the tumor in the rectum (n = 96, 47.76%). Examining coagulation factors, univariate Cox analysis of colon cancer patients showed that activated partial thromboplastin time (p = 0.020) was significantly associated with overall survival, but we could not prove it in multivariate analysis. In colon cancer patients, neutrophil-to-lymphocyte ratio (NLR, p < 0.001) was positively correlated with tumor size and had significant association (χ2  = 5.48, p = 0.019, df = 1) with perineural invasion. Univariate and multivariate Cox analysis of colon cancer patients showed that NLR (p = 0.011 and p = 0.048) was significantly associated with disease-free survival (DFS). CONCLUSION: NLR was proved to be an independent prognostic factor for DFS in patients with non-metastatic colon cancer. NLR might help to recognize the high-risk patients between patients with the same tumor-node-metastasis stage and could help with the decision on adjuvant chemotherapy. Since the biomarkers in preoperative blood tests are habitually evaluated, NLR could be an inexpensive prognostic marker that can be easily assessed in clinical practice.


Assuntos
Neoplasias Colorretais , Testes Hematológicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos
15.
Future Oncol ; 18(7): 793-805, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34854318

RESUMO

Aim: This study aimed to identify specific and sensitive exosomal miRNAs in diagnosing patients with colorectal cancer (CRC). Methods: Serum exosomes were isolated from 175 CRC patients and 172 healthy donors by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was detected by quantitative PCR and the results analyzed by receiver operating characteristic analysis to illuminate the diagnostic accuracy. Results: Both exosomal miR-377-3p and miR-381-3p were downregulated in CRC patients as well as in early-stage patients compared with healthy donors; they could serve as circulating biomarkers of diagnosis, including early diagnosis, for CRC, possessing favorable diagnostic efficiency. Conclusion: Exosomal miR-377-3p and miR-381-3p levels were downregulated in CRC patients and may be useful as novel and specific biomarkers for the diagnosis of CRC, especially early-stage CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Exossomos/metabolismo , MicroRNAs/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Linhagem Celular Tumoral , Neoplasias Colorretais/sangue , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
16.
Tumori ; 108(1): 56-62, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33393453

RESUMO

INTRODUCTION: Recently, a new inflammatory marker, the advanced lung cancer inflammation index (ALI), was reported as a prognostic marker in patients with several cancers. We aimed to investigate the prognostic value of ALI in patients with colorectal cancer liver metastases (CLM) undergoing surgery. METHODS: From June 2009 to June 2018, 141 patients underwent a surgery for CLM at Ajou University Hospital, of whom 132 without extrahepatic metastases, systemic inflammatory diseases, or immune system diseases were enrolled in this study. The ALI was calculated using the following formula: ALI = body mass index × serum albumin/neutrophil-to-lymphocyte ratio. The patients were divided into high (n = 32) and low (n = 100) ALI groups according to the preoperative optimal cutoff value of 70.40 that was determined by X-tile software. RESULTS: Patients with low ALI had a significantly worse overall survival (OS) compared to the high ALI group (p = 0.010). Multivariate analysis showed that ALI and carcinoembryonic antigen (CEA) were independently associated with OS (p = 0.009 and p = 0.042, respectively). Among the patients with CEA >5 ng/mL, the low ALI group had a significantly worse OS compared to the high ALI group (p = 0.013). CONCLUSION: Preoperative ALI was a prognostic factor in patients with CLM undergoing surgery. In particular, the prognostic impact of ALI was more prominent in the patients with CEA >5 ng/mL.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Inflamação/sangue , Neoplasias Hepáticas/sangue , Neoplasias Pulmonares/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutrófilos/metabolismo , Prognóstico , Albumina Sérica/metabolismo
17.
Biochem Pharmacol ; 196: 114595, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33964280

RESUMO

Colorectal cancer (CRC) is a highly prevalent malignancy. Previous studies suggested that cholesterol might play a signficant role in malignant transformation and proliferation. Non-cholesterol sterols (NCS), which are transported by serum lipoproteins alongside cholesterol, are regarded as cholesterol synthesis and absorption markers. Quantification of NCS in serum and HDL fraction (NCSHDL), could provide a better insight into the cholesterol metabolism. The aim of this study was to examine the status of cholesterol synthesis and cholesterol absorption markers in serum and HDL fraction and explore their interrelation in CRC patients. Current study was designed as observational, case-control study. The study included 73 CRC patients and 95 healthy subjects. NCS and NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCSHDL concentrations (P<0.001 for desmosterolHDL; P<0.05 for lathosterolHDL, P=0.001 for campesterolHDL, P<0.001 for ß-sitosterolHDL). NCSHDL/NCS (P<0.005 for desmosterolHDL/desmosterol; P<0.05 for lathosterolHDL/lathosterol; P<0.001 for both ß-sitosterolHDL/ß-sitosterol and campesterolHDL/campesterol) and synthesis to absorption ratio (CSI/CAI) (P<0.005) were increased in CRC patients. Additionally, low serum concentrations of desmosterol (P<0.001; OR=0.329; 95%CI (0.199-0.542)) and campesterol (P<0.001; OR=0.540; 95%CI (0.424-0.687)) were independent predictors of CRC presence. Our data suggest that cholesterol homeostasis in CRC is shifted towards increased synthesis. Relative abundance of NCS in HDL particles is increased, suggesting the possible overproduction of cholesterol precursors in peripheral tissues.


Assuntos
Biomarcadores Tumorais/sangue , Colesterol/sangue , Neoplasias Colorretais/sangue , Esteróis/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Cancer Epidemiol Biomarkers Prev ; 31(1): 293-295, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758968

RESUMO

BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.


Assuntos
Adenoma/sangue , Pólipos do Colo/sangue , Neoplasias Colorretais/sangue , Hormônios Esteroides Gonadais/sangue , Idoso , California , Estudos de Casos e Controles , Colonoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
20.
Am J Gastroenterol ; 117(1): 158-166, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34730560

RESUMO

INTRODUCTION: Statin use has been examined as a potential chemopreventive strategy against colorectal cancer (CRC). Previous studies have not been able to investigate this topic with adequate follow-up time or disentangle the effects of statin use and total cholesterol level. We investigated prospectively this topic. METHODS: Eligible participants (100,300 women and 47,991 men) in the Nurses' Health Study and Health Professionals Follow-Up Study were followed for up to 24 years. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: We documented 2,924 incident CRC cases during follow-up. In fully adjusted analyses, longer duration of statin use was associated with higher risk of colon cancer (hazard ratios, the 95% confidence interval was 1.09, 0.95-1.25 for 1-5 years; 1.16, 0.99-1.36 for 6-10 years; 1.08, 0.81-1.44 for 11-15 years; 1.85, 1.30-2.61 for >15 years; vs never users, P = 0.004 for trend) rather than rectal cancer. The risk elevation was driven by proximal colon cancer (1.16, 0.98-1.38 for 1-5 years; 1.19, 0.98-1.45 for 6-10 years; 1.25, 0.89-1.74 for 11-15 years; 2.17, 1.46-3.24 for >15 years; vs never users, P = 0.001 for trend) rather than distal colon cancer. The results remained robust in analyses among participants with hypercholesterolemia or who never received screening. Total cholesterol level was not associated with CRC risk. DISCUSSION: This study does not support benefit of statin use in CRC chemoprevention or any association between total cholesterol level and CRC risk. On the contrary, long-term statin use may be associated with increased colon cancer risk (driven by proximal colon cancer).


Assuntos
Quimioprevenção/métodos , Colesterol/sangue , Neoplasias Colorretais/prevenção & controle , Previsões , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Medição de Risco/métodos , Adulto , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...