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1.
Khirurgiia (Mosk) ; (10): 36-43, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33047584

RESUMO

OBJECTIVE: To determine the effect of intraperitoneal chemotherapy (IPC) with mitomycin C on expression of intraperitoneal cancer cells markers in patients with T4 colon cancer. MATERIAL AND METHODS: For the period from January 2019 to April 2020, 65 patients with T4 colon cancer were included in prospective comparative study. There were 46 patients in the main group and 19 patients in the control group. In the main group, surgical procedure was followed by IPC with mitomycin C. No IPC was performed in the control group. An effectiveness of IPC was evaluated using CD133, CD24, CD26, CD44, CD184 markers expression in peritoneal lavages. RESULTS: Significant between-group differences were observed for CD133 (p=0.0168), CD24 (p=0.0455) and CD44 (p=0.0012). There was a tendency to decrease in the level of CD184 expression in both groups in the second lavage (p=0.0605). CONCLUSION: IPC in patients with T4 colon cancer can reduce the expression and proliferative potential of free cancer cells.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Mitomicina/administração & dosagem , Antígeno AC133/análise , Antígeno AC133/biossíntese , Líquido Ascítico/química , Antígeno CD24/análise , Antígeno CD24/biossíntese , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Dipeptidil Peptidase 4/análise , Dipeptidil Peptidase 4/biossíntese , Humanos , Receptores de Hialuronatos/análise , Receptores de Hialuronatos/biossíntese , Infusões Parenterais , Lavagem Peritoneal , Estudos Prospectivos , Receptores CXCR4/análise , Receptores CXCR4/biossíntese
2.
Nat Commun ; 11(1): 4469, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901013

RESUMO

Dissecting tumor heterogeneity is a key to understanding the complex mechanisms underlying drug resistance in cancers. The rich literature of pioneering studies on tumor heterogeneity analysis spurred a recent community-wide benchmark study that compares diverse modeling algorithms. Here we present FastClone, a top-performing algorithm in accuracy in this benchmark. FastClone improves over existing methods by allowing the deconvolution of subclones that have independent copy number variation events within the same chromosome regions. We characterize the behavior of FastClone in identifying subclones using stage III colon cancer primary tumor samples as well as simulated data. It achieves approximately 100-fold acceleration in computation for both simulated and patient data. The efficacy of FastClone will allow its application to large-scale data and clinical data, and facilitate personalized medicine in cancers.


Assuntos
Algoritmos , Variações do Número de Cópias de DNA , Neoplasias/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Biologia Computacional/métodos , Simulação por Computador , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Modelos Genéticos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Filogenia , Medicina de Precisão , Análise de Sequência de DNA
3.
Nat Commun ; 11(1): 4551, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917870

RESUMO

Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellular expression patterns of ciRS-7 in colon cancer and show that ciRS-7 is completely absent in the cancer cells, but highly expressed in stromal cells within the tumor microenvironment. Additionally, our data suggest that this generally apply to classical oncogene-driven adenocarcinomas, but not to other cancers, including malignant melanoma. Moreover, we find that correlations between circRNA and mRNA expression, which are commonly interpreted as evidence of a ceRNA function, can be explained by different cancer-to-stromal cell ratios among the studied tumor specimens. Together, these results have wide implications for future circRNA studies and highlight the importance of spatially resolving expression patterns of circRNAs proposed to function as ceRNAs.


Assuntos
Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Circular/metabolismo , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genética , Idoso , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oncogenes/genética , Estudos Prospectivos , RNA Circular/genética , RNA Longo não Codificante/genética , Análise Espacial
4.
Medicine (Baltimore) ; 99(37): e22170, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925784

RESUMO

BACKGROUND: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. METHODS: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. RESULTS: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. CONCLUSIONS: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Fator Regulador 1 de Interferon/imunologia , Linfócitos T/imunologia , Biomarcadores Tumorais , Linfócitos T CD8-Positivos/metabolismo , Bases de Dados Genéticas , Células Dendríticas/metabolismo , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/imunologia , Estadiamento de Neoplasias , Prognóstico , Microambiente Tumoral
5.
Chem Biol Interact ; 330: 109236, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866467

RESUMO

A series of novel pyrrolopyrimidine urea derivatives were synthesized and evaluated for their anticancer activity against colon cancer cell lines. Compounds showed the remarkable cytotoxic activity on HCT-116 wt cell line. The most potent compound 4c (IC50 = 0.14 µM) induced apoptosis in HCT-116 wt and HCT-116 p53-/- cell lines. Otherwise, treatment of HCT-116 BAX-/-BAK-/- cells with compound 4c didn't lead to activation of apoptosis, suggesting that compound 4c induces apoptotic cell death by activating BAX/BAK-dependent pathway. Moreover, while the compound 4c increase the activation of caspase-3 and caspase-9 levels in HCT-116 wt and HCT-116 p53-/- cells, caspase-3 or caspase-9 activation was not observed in HCT-116 BAX-/-BAK-/- cells. In addition, compound 4c induced mitochondrial apoptosis in cells grown as oncospheroids, which better mimic the in vivo milieu of tumors. 4c treatment also activated JNK along with inhibition of prosurvival kinases such as Akt and ERK 1/2 in HCT-116 wt and HCT-116 p53 -/- cells as well as in HCT-116 BAX-/-BAK-/- cells. Notably, our results indicated that compound 4c induced mitochondrial apoptosis through activation p53-independent apoptotic signaling pathways.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Pirimidinas/farmacologia , Pirróis/farmacologia , Proteína Supressora de Tumor p53/fisiologia , Caspase 3/genética , Caspase 9/genética , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Técnicas de Inativação de Genes , Células HCT116 , Humanos , Mitocôndrias/metabolismo , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Proteína Supressora de Tumor p53/genética , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína X Associada a bcl-2/genética
6.
Anticancer Res ; 40(9): 5159-5170, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878804

RESUMO

BACKGROUND/AIM: The aim of this study was to elucidate the possibility of sensitizing colon cancer cells to the chemotherapeutic drug SN38 and investigate its mechanism of action after combined treatment with electroporation (EP). MATERIALS AND METHODS: Cells were treated with SN38, EP and their combination for 24/48 h. The cell viability, actin cytoskeleton integrity, mitochondrial superoxide, hydroperoxides, total glutathione, phosphatidyl serine expression, DNA damages and expression of membrane ABC transporters were analyzed using conventional analytical tests. RESULTS: The combination of EP and SN38 affected cell viability and cytoskeleton integrity. This effect was accompanied by: (i) high production of intracellular superoxide and hydroperoxides and depletion of glutathione; (ii) increased DNA damage and apoptotic/ferroptotic cell death; (iii) changes in the expression of membrane ABC transporters - up-regulation of SLCO1B1 and retention of SN38 in the cells. CONCLUSION: The anticancer effect of the combined treatment of SN38 and EP is related to changes in the redox-homeostasis of cancer cells, leading to cell death via apoptosis and/or ferroptosis. Thus, electroporation has a potential to increase the sensitivity of cancer cells to conventional anticancer therapy with SN38.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Oxirredução , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Dano ao DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Imunofluorescência , Glutationa/metabolismo , Humanos , Modelos Biológicos , Espécies Reativas de Oxigênio/metabolismo
7.
Anticancer Res ; 40(10): 5611-5620, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988885

RESUMO

BACKGROUND/AIM: Cancer stem cell characteristics and drug resistance of colorectal cancer are associated with failure of cancer treatment. In this study, we investigated the effects of PrPC on cancer stem cell characteristics, migration, invasion, and drug resistance of 5FU-resistant CRC cells. MATERIALS AND METHODS: PrPC negative and PrPC positive cells were isolated from 5FU-resistant CRC cells using magnetic activated cell sorting. Sphere formation, cancer stem cell marker expression, migration, invasion, and drug resistance were analyzed. RESULTS: PrPC positive cells showed increased sphere formation capacity and increased expression of cancer stem cell markers compared to PrPC negative cells. In addition, PrPC positive cells showed increased migration, invasion and drug resistance compared to PrPC negative cells. Furthermore, knockdown of PrPC abolished these effects. CONCLUSION: PrPC expression is important in CRC cell behavior, such as sphere formation, migration, invasion, and drug resistance. PrPC is an important therapeutic target for the treatment of CRC.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Proteínas Priônicas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos
8.
BMC Bioinformatics ; 21(1): 398, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907537

RESUMO

BACKGROUND: Protein biomarkers play important roles in cancer diagnosis. Many efforts have been made on measuring abnormal expression intensity in biological samples to identity cancer types and stages. However, the change of subcellular location of proteins, which is also critical for understanding and detecting diseases, has been rarely studied. RESULTS: In this work, we developed a machine learning model to classify protein subcellular locations based on immunohistochemistry images of human colon tissues, and validated the ability of the model to detect subcellular location changes of biomarker proteins related to colon cancer. The model uses representative image patches as inputs, and integrates feature engineering and deep learning methods. It achieves 92.69% accuracy in classification of new proteins. Two validation datasets of colon cancer biomarkers derived from published literatures and the human protein atlas database respectively are employed. It turns out that 81.82 and 65.66% of the biomarker proteins can be identified to change locations. CONCLUSIONS: Our results demonstrate that using image patches and combining predefined and deep features can improve the performance of protein subcellular localization, and our model can effectively detect biomarkers based on protein subcellular translocations. This study is anticipated to be useful in annotating unknown subcellular localization for proteins and discovering new potential location biomarkers.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/patologia , Proteínas/metabolismo , Neoplasias do Colo/metabolismo , Bases de Dados de Proteínas , Humanos , Imuno-Histoquímica , Aprendizado de Máquina , Proteínas/classificação
9.
Anticancer Res ; 40(10): 5405-5409, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988860

RESUMO

AIM: To investigate the clinical significance of ATP-binding cassette transporter 11 (ABCC11) protein expression in colon cancer. MATERIALS AND METHODS: One hundred thirty nine patients with colon cancer resection between 2009 and 2011 were enrolled. The relationship with immunohistochemical ABCC11 staining and clinicopathological factors was retrospectively analyzed. RESULTS: Median age was 70 years including 67 males and 72 females. The patients with Stage 0, 1, 2, 3a and 4 were 4, 20, 43, 35, 7 and 30, respectively. The patients with curability (Cur) A, B and C were 109, 11 and 19, respectively. Positive expression of ABCC11 was observed in 31 patients (22.3%). There were no significant differences regarding age, gender, location, serum tumor markers, T category, lymphatic invasion and stage in relation to ABCC11 protein expression. Cases with node metastasis and venous invasion as well as unresectable cases were significantly more often found negative for ABCC11 protein (p=0.0246, 0.0285 and 0.0422, respectively). Concerning the 3 year disease free survival (DFS) and the 5 year overall survival (OS) in Stage 2/3 and in Stage 3 with adjuvant chemotherapy, no significant differences were found. However, OS in ABCC11 negative cases was 81.1%, which was significantly lower compared to positive cases, where OS was 96.2%. CONCLUSION: There was significant correlation with ABCC11 expression and lymph node metastasis, venous invasion and curability. The prognosis in ABCC11 negative cases was poor because of increased cases without curative resection.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Metástase Linfática/genética , Idoso , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
10.
BMC Gastroenterol ; 20(1): 269, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32799796

RESUMO

BACKGROUND: Cancer patients are at increased risk of novel coronavirus disease 2019 (COVID-19). Currently, surgeries for cancer patients with COVID-19 are generally suggested to be properly delayed. CASE PRESENTATION: We presented a 69-year-old Chinese female colon cancer patient with COVID-19, the first case accepted the surgical treatment during the pandemic in China. The patient developed a fever on January 28, 2020. After treatments with Ceftriaxone and Abidol, her fever was not moderated yet. A repeat chest computed tomography (CT) scan showed significantly exacerbated infectious lesions with a positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid. An abdomen CT scan indicated the tumor of ascending colon with local wrapped changes. She was diagnosed with 'Severe novel coronavirus pneumonia' and 'Incomplete bowel obstruction: Colon cancer?'. After actively anti-inflammatory and anti-viral therapies, a right colectomy with lymph node dissection was performed on March 11, followed by a pathological examination. The patient successfully recovered from COVID-19 pneumonia and incomplete bowel obstruction after surgery without any postoperative related complications and was discharged on the 9th day after operation. Significant degeneration, necrosis and slough of focal intestinal and colonic mucosal epithelial cells were observed under microscope. No surgeons, nurses or anesthetists in our team were infected with SARS-CoV-2. CONCLUSIONS: It is meaningful and imperative to share our experience of protecting health care personnels from SARS-CoV-2 infection and providing references for optimizing treatment of cancer patients, at least for the operative intervention with absolute necessity or surgical emergency, during the outbreak of COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Colectomia/métodos , Neoplasias do Colo , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Colo Ascendente/diagnóstico por imagem , Colo Ascendente/patologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Neoplasias do Colo/fisiopatologia , Neoplasias do Colo/cirurgia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Feminino , Humanos , Controle de Infecções/métodos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
11.
Cancer Invest ; 38(7): 406-414, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32762373

RESUMO

BACKGROUND: Programmed death 1 (PD-1) and its ligand PD-L1 play a key dysfunction of T lymphocytes. The purpose of this study was to assess and compare the prognostic role of tumor- TILs and its relationship with PD-L1 expression in stage II and III colon cancer. METHODS: Immunohistochemisty was used to assess the densities of CD8+, CD4+, and FOXP3+ cells, and PD-L1 expression in intraepithelial tumor site from 58 stage II and III colon cancers. These were evaluated for association with histopathologic features and overall survival. RESULTS: PD-L1-positive tumors contained a higher number of CD8+ TILs with statistical significance (p = 0.001). CD4+ TILs showed positive correlation with PD-L1 expression (p = 0.034). There were no associations between PD-L1 expression and FOXP3+ TILs. Microsatellite instability (MSI)-high status (p = 0.001; Odd ration 18.0; 95% CI = 4.3-74.8) was the strongest prognostic factor along with mucinous/poor cell differentiation, CD8 and right tumor location was associated with PD-L1 expression (p = 0.024, 0.035 and 0.033, respectively). CONCLUSION: This study demonstrated that PD-L1 expression was associated with MSI-high, increased CD8+ TILs, mucinous and poor cell differentiation, and right-sided tumor location.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Sobrevida
12.
DNA Cell Biol ; 39(10): 1825-1837, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32799546

RESUMO

The objective of this study was to identify the key circular RNAs (circRNAs) related to the development of colon cancer. High-throughput RNA sequencing on eight early-stage (ES) and eight later stage (LS) colon tumor tissues, and eight normal tissues, was performed. Differentially expressed circRNAs and differentially expressed mRNAs were identified. Functional enrichment analysis and the miRNA-circRNA-mRNA network were performed. In addition, the differential expression levels of key circRNAs were verified using real-time quantitative PCR (qPCR). In total, 408, 472, and 278 differentially expressed circRNAs were identified in ES versus normal control (N), LS versus N, and LS versus ES groups, respectively. Functional enrichment analysis showed that circ_052666 was significantly enriched in "extracellular matrix/receptor interaction"; circ_022743 was remarkably enriched in "neurotrophin signaling pathway"; and circ_004452 was observably enriched in "TGF-ß signaling pathway." Moreover, key miRNA-circRNA-mRNA relationships, such as hsa-miR-29b/c-3p-circ_052666-COL1A1 and hsa-miR-1294-circ_004452-left-right determination factor 1 (LEFTY1), were identified. Furthermore, qPCR showed consistent results with RNA sequencing. Our findings indicate that key circRNAs, such as circ_022743, circ_052666, and circ_004452, may be involved in colon cancer development, and could be used as potential biomarkers for the diagnosis and treatment of this disease.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , RNA Circular/genética , Transcriptoma , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , RNA Circular/metabolismo
13.
Gene ; 763: 145072, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-32827679

RESUMO

Colon cancer is one of the most common diseases in the world with both a high incidence and high mortality. PLAC1 is activated and expressed in many cancers. We aim to explore the relationship between PLAC1 expression and prognosis in colon cancer patient. The RNA-Seq expression data and clinical information of colon cancer were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed PLAC1 was obtained by the Wilcoxon signed-rank test; the significance difference being that PLAC1 was more highly expressed in tumor rather than normal tissue (p < 0.01). Then patients were classified into high and low risk groups by different risk scores, and the Kaplan-Meier survival analysis showed that colon cancer patients with a high PLAC1 expression had a poorer prognosis than low PLAC1 expression patients (p = 0.0031). Next, in analyzing the clinical pathology associated with PLAC1 expression, logistic regression showed that PLAC1 was expressed high in stage (OR = 4.11 for I vs. IV), lymph nodes (OR = 1.73 for N0 vs. N1+), distant metastasis (OR = 2.8 for M0 vs. M1), and status (OR = 22.81 for normal vs. tumor). Univariate and multivariate cox analyses were employed to identify that PLAC1 could be regarded as an independent prognostic factor. Univariate cox analysis showed PLAC1 had a correlation to overall survival (OS) (HR: 0.46, 95% CI: 0.28-0.77, p = 0.003). Multivariate cox analysis revealed that PLAC1 (HR: 0.51, 95% CI: 0.30-0.86, p = 0.012) could be regarded as an Independent prognostic factor. We also used quantitative real-time polymerase chain reaction (qRT-PCR) to test if PLAC1 was differently expressed in cell lines. The qRT-PCR obtained the significant results that PLAC1 expressed high in colon cancer cell lines (p < 0.05). Finally, Gene Set Enrichment Analysis (GSEA) was utilized to show 14 enriched signaling pathways. Our study discovered that high expression of PLAC1 predicts poor prognosis in colon cancer patients, providing a new biomarker, which can assist physicians in finding new diagnostic and therapy methods for colon cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Proteínas da Gravidez/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Proteínas da Gravidez/metabolismo
14.
J Oleo Sci ; 69(8): 929-939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759551

RESUMO

Glucosylceramide (GlcCer), a major sphingolipid in plants and fungi, is known to have food functions, such as preventing intestinal impairment and enhancing the moisture content of skin. This study investigated the influence of fermentation on the composition and function of lipophilic components containing GlcCer in plant-based foods; we compared the effects of ethanol extracts from sake rice (SR) and sake lees (SL) on colon impairment in mice. GlcCer and ceramide (Cer) levels in SL were much higher than those in SR, and GlcCer in SL contained 9-methyl-trans-4,trans-8-sphingadienine as a fungi-specific sphingoid base. 1,2-dimethylhydrazine (DMH) treatment markedly increased the formation of aberrant crypt foci (ACF) and the levels of TNF-α and lipid oxidation in mice colons. However, dietary SR or SL significantly suppressed these DMH-induced changes, and SR demonstrated stronger effects than SL. In addition, dietary SR or SL suppressed the expression of apoptotic and anti-apoptotic proteins induced by DMH treatment. This study suggests that SR or SL intake could reduce colon ACF formation via the suppression of inflammation and oxidation-induced cell cycle disturbances. When compared to SR, the weaked effects of SL rich in GlcCer may be the result of the changes in sphingolipid composition (sphingoid base and Cer) and differences in the concentration of other bioactive compounds produced or digested during fermentation.


Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Neoplasias do Colo/prevenção & controle , Glucosilceramidas/análise , Glucosilceramidas/farmacologia , Oryza/química , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Vinho/análise , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Administração Oral , Animais , Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Etanol , Feminino , Fermentação , Glucosilceramidas/administração & dosagem , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
15.
Niger J Clin Pract ; 23(8): 1048-1053, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788480

RESUMO

Aims: To describe the clinical characteristics, colonoscopic features, histological findings, dysplasia patterns, and clinical outcome of endoscopically detected colonic polyps in the Saudi population. Methods: This retrospective record review was conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, on patients who underwent colonoscopy between 2005 and 2015. Patients with colorectal cancer were excluded. Data were analyzed using SPSS software. Results: Among 211 patients recruited, 66.8% were males and 66.2% were Saudi. Single polyps were detected in 45.5% of cases, while 29.9%, 18%, and 6.6% had 2, 3, and 4 polyps, respectively. Regarding the size, 81%, 17%, and 2% of the polyps were <1 cm, 1-2 cm, and >2 cm, respectively. The endoscopic examination revealed that 16.4% of the polyps were pedunculated, 82.6% were sessile, and 1% were sessile and pedunculated. About 45%, 30%, 21%, and 6.6% of the polyps were located at the rectum/sigmoid, left colon, right colon, and transverse/ascending colon, respectively. Histologically, 68.6% of polyps were adenomatous and 21.3% were non-adenomatous. Mild dysplasia was detected in almost half of the studied sample (42.3%) while moderate and severe grades of dysplasia were demonstrated in 19.2% and 38.5% of the examined polyps. Surgical intervention was required in 8.1% of cases. Conclusion: Single small-sized sessile polyps of adenomatous type and mild dysplasia are the most common polyps in the Saudi population. Sigmoid/rectum is the most common site affected, and the outcome of polyps is generally favorable.


Assuntos
Adenoma/patologia , Colo Ascendente/diagnóstico por imagem , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Colonoscopia/métodos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Colo Ascendente/patologia , Neoplasias do Colo/epidemiologia , Pólipos do Colo/epidemiologia , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/epidemiologia , Estudos Retrospectivos , Arábia Saudita , Distribuição por Sexo
17.
Yonsei Med J ; 61(7): 572-578, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32608200

RESUMO

PURPOSE: Wnt and mammalian target of rapamycin (mTOR) are major molecular signaling pathways associated with the development and progression of tumor, as well as the maintenance and proliferation of cancer stem cells (CSCs), in colorectal cancer (CRC). Identifying patients at risk of poor prognosis is important to determining whether to add adjuvant treatment in stage II CRC and thus improve survival. In the present study, we evaluated the prognostic value of Wnt, mTOR, and CSC markers as survival predictors in stage II CRC. MATERIALS AND METHODS: We identified 148 cases of stage II CRC and acquired their tumor tissue. Tissue microarrays for immunohistochemical staining were constructed, and the expressions of CD166, CD44, EphB2, ß-catenin, pS6 were evaluated using immunohistochemical staining. RESULTS: The expressions of CD166 (p=0.045) and pS6 (p=0.045) and co-expression of pS6/CD166 (p=0.005), pS6/CD44 (p=0.042), and pS6/CD44/CD166 (p=0.013) were negatively correlated with cancer-specific survival. Cox proportional hazard analysis showed the combination of CD166/pS6 [hazard ratio, 9.42; 95% confidence interval, 2.36-37.59; p=0.002] to be the most significant predictor related with decreased cancer-specific survival. In addition, co-expression of CD44/CD166 (p=0.017), CD166/ß-catenin (p=0.036), CD44/ß-catenin (p=0.001), and CD44/CD166/ß-catenin (p=0.001) were significant factors associated with liver metastasis. CONCLUSION: Specific combinations of CSC markers and ß-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Serina-Treonina Quinases TOR/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Receptores de Hialuronatos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/transplante , Prognóstico , Transdução de Sinais , Serina-Treonina Quinases TOR/análise , beta Catenina
18.
Anticancer Res ; 40(7): 4029-4032, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620648

RESUMO

The synchronous diagnosis of two or more primary malignancies in a patient is overall rare. This is a case report of a 70-year-old female with a history of skin squamous cell carcinoma presenting with occult hematochezia. Colonoscopy and biopsy results confirmed a microsatellite stable (MMS) adenocarcinoma in the ascending colon, and subsequent computed tomography (CT) scans identified a 3.2 cm right colonic mass and a 5.0 cm mass in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) confirmed the presence of pancreatic ductal adenocarcinoma (PDAC). The patient underwent neo-adjuvant FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin) chemotherapy prior to the simultaneous distal pancreatectomy and right hemicolectomy for both pancreatic and colonic tumors. The pathology diagnoses included moderately differentiated pancreatic ductal carcinoma (PDAC) with histiocyte-like features (tumor stage: ypT3N1M0) and moderately differentiated colonic adenocarcinoma, intestinal type (tumor stage: ypT3N0M0). To the best of our knowledge, this is the first documented case of synchronous primary colonic adenocarcinoma and PDAC in the English literature.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patologia , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Carcinoma de Células Escamosas , Neoplasias do Colo/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Primárias Múltiplas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Cutâneas
19.
Anticancer Res ; 40(7): 4053-4057, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620652

RESUMO

BACKGROUND/AIM: As of 2020, adenocarcinoma arising in the ileocecal valve (ICV-A) has been examined along with cecal and right colon cancer (RCC) under the collective heading "ileocecal" tumor. We propose a new classification system for this cancer. PATIENTS AND METHODS: We retrospectively analyzed RCC patients from 2003 to 2019. The scheme was: i) Type I cancer for adenocarcinomas residing in ICV; ii) Type II, if they reside 1 to 5 mm from ICV; iii) Type III, 6 mm to 10 mm from ICV; iv) Type IV, at 1,1 to 5 cm; v) Type V, at more than 5 cm (ascending colon cancer). RESULTS: Of 689 hemicolectomized patients, there were 91 (13.2%) Type I, 87 Type II (12.6%), 38 (5.5%) Type III, 157 (22.8%) Type IV and 314 (45.6%) Type V. Each type was associated with at least one clinicopathologic feature. CONCLUSION: ICV-A was classified into five types (I-V) according to the distance from ICV. Further studies are needed in order to corroborate our findings.


Assuntos
Adenocarcinoma/classificação , Neoplasias do Ceco/classificação , Neoplasias do Colo/classificação , Valva Ileocecal/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias do Ceco/patologia , Neoplasias do Ceco/cirurgia , Colectomia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos
20.
Anticancer Res ; 40(8): 4331-4341, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727761

RESUMO

BACKGROUND/AIM: Adjuvant chemotherapy is recommended for a subgroup of colon cancer patients based on patient and tumour characteristics. Population-based data on the adoption of the prevailing guideline recommendations including the assessment of tumour mismatch repair (MMR) status are limited, while variations in treatment strategies may influence patient outcomes. Therefore, the aim of the study was to assess practice variation in adjuvant chemotherapy administration in colon cancer patients. PATIENTS AND METHODS: We examined the association between patient, demographic and tumour characteristics on the odds of being treated with adjuvant chemotherapy in a random sample of adult stage II-III colon cancer patients from the Dutch National Cancer Registry (2008-2015) and assessed its association with survival. RESULTS: The study population consisted of 2,044 patients of whom 18% (79 out of 450) were high-risk stage II and 65% (645 out of 997) were stage III colon cancer and received adjuvant chemotherapy. Chemotherapy administration differed between individual hospitals (high-risk stage II: 0-39%; p=0.01; stage III: 50-78%; p=0.06). Type of hospital (teaching versus academic) and the presence of a pT4 tumour were positively associated (high-risk stage II), and bowel perforation and examined regional lymph nodes (<10) were negatively associated (stage III) with adjuvant treatment. Higher age was associated with non-administration of adjuvant chemotherapy for both stages. Tumour MMR-status assessment increased from 9% to 23% (p<0.001), but 62% of high-risk stage II and 13% of stage III patients did not undergo guideline-recommended MMR-status testing. Adjuvant chemotherapy was correlated with survival for stage III (HR=0.4; 95%CI=0.3-0.5) but not for high-risk stage II patients (HR=1.2; 95%CI=0.7-2.2). CONCLUSION: Significant practice variation in the adjuvant treatment of colon cancer on hospital level was demonstrated, predominantly in high-risk stage II patients. The implementation of MMR testing was suboptimal. We recommend continuous monitoring of treatment patterns using population-based data, which should facilitate hospital auditing and improve guideline implementation and quality of care for colon cancer patients.


Assuntos
Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Idoso , Estudos de Coortes , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Sistema de Registros , Análise de Sobrevida
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