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1.
Cancer Rep (Hoboken) ; 7(5): e2003, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38703000

RESUMEN

BACKGROUND: Mid-rectal cancer treatment traditionally involves conventional laparoscopic-assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. AIMS: To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long-term prognosis between NOSES and CLAR groups. MATERIALS & METHODS: A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. RESULTS: The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. CONCLUSION: While long-term outcomes (overall survival, disease-free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid-rectal cancer treatment, while maintaining similar long-term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long-term results.


Asunto(s)
Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Neoplasias del Recto , Humanos , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Masculino , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Persona de Mediana Edad , Anciano , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tiempo de Internación/estadística & datos numéricos , Resultado del Tratamiento , Calidad de Vida , Puntaje de Propensión
2.
J Tradit Chin Med ; 43(6): 1219-1226, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37946484

RESUMEN

OBJECTIVE: To investigate the bioactive compounds of Chaihu (Radix Bupleuri Chinensis) (RB) on glaucomatous optic atrophy (GOA), and to study the pharmacological mechanism. METHODS: We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to bioactive compounds and GOA were also obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses were performed to investigate the potential mechanism of RB against GOA. Subsequently, the main bioactive compounds of RB and targets of GOA were docked by Autodock software. Moreover, a GOA model of retinal ganglion cells (RGCs) induced by cobalt chloride was established to verify the effect of RB on GOA. RESULTS: There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA. The compound-target network mainly contained 17 compounds and 46 corresponding targets, and the key targets consisted of interleukin-6 (IL-6), hypoxia inducible factor-1α (HIF1A), Caspase-3, estrogen receptor alpha (ESR1), MYC proto-oncogene (MYC), and vascular endothelial growth factor A (VEGFA). Forty-nine significantly enriched GO terms, and 134 KEGG signaling pathways were identified (P < 0.05), including HIF-1, tumor necrosis factor, VEGF, prolaction, and other signaling pathways. Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6. Furthermore, experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner. The RB extract also suppressed the expression of Bax, Caspase-3, and Caspase-9 and regulated malonaldehyde, superoxide dismutase, and glutathione peroxide by inhibiting the IL-6/HIF-1α signaling pathway. CONCLUSIONS: The present study provided insights into the mechanism of RB on GOA. RB mainly reverses GOA by inhibiting the IL-6/HIF-1α signaling pathway.


Asunto(s)
Medicamentos Herbarios Chinos , Interleucina-6 , Humanos , Interleucina-6/genética , Caspasa 3 , Factor A de Crecimiento Endotelial Vascular , Simulación del Acoplamiento Molecular , Extractos Vegetales , Hipoxia
3.
Mol Cancer ; 22(1): 157, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37770864

RESUMEN

BACKGROUND: Although colonoscopy is the standard screening test for colorectal cancer (CRC), its use is limited by a poor compliance rate, the need for extensive bowel preparation, and the risk of complications. As an alternative, an FDA-approved stool-based DNA test, Cologuard, has demonstrated satisfactory detection performance for CRC, but its compliance rate remains suboptimal, primarily attributable to individuals' reluctance to provide stool samples. METHODS: We developed a noninvasive blood-based CRC test, ColonSecure, based on cell-free DNA containing cancer-specific CpG island methylation patterns. We initially screened publicly available datasets for differentially methylated CpG sites in CRC with prediction potential. Subsequently, we performed two sequential bisulfite-free methylation sequencing on blood samples obtained from CRC patients and non-cancer controls. Through rigorous evaluation of each marker and machine learning-assisted feature selection, we identified 149 hypermethylated markers from over 193,000 CpG sites. These markers were then utilized to construct the ColonSecure model, enabling accurate CRC detection. RESULTS: We validated the efficacy of our cell-free DNA methylation-based blood test for CRC screening with 3493 high-risk individuals identified from 114,136 urban residents. The ColonSecure test identified 89 out of 103 CRC patients diagnosed by the follow-up colonoscopy, outperforming CEA, CRP, and CA19-9 (with a sensitivity of 86.4% compared to 45.6%, 39.8%, and 25.2% for CEA, CRP, and CA19-9 respectively; an AUROC of 0.956 compared to an AUROC of < 0.77 for other methods). CONCLUSION: Our observations emphasize the potential of our multiple cfDNA methylation marker-based test for CRC screening in high-risk populations.


Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , Humanos , Metilación de ADN , Ácidos Nucleicos Libres de Células/genética , Estudios Prospectivos , Antígeno CA-19-9 , Detección Precoz del Cáncer , Islas de CpG , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Biomarcadores de Tumor/genética
4.
Cell Biosci ; 13(1): 138, 2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37507776

RESUMEN

BACKGROUND: Gamma sensory stimulation may reduce AD-specific pathology. Yet, the efficacy of alternating electrical current stimulation in animal models of AD is unknown, and prior research has not addressed intensity-dependent effects. METHODS: The intensity-dependent effect of gamma electrical stimulation (GES) with a sinusoidal alternating current at 40 Hz on Aß clearance and microglia modulation were assessed in 5xFAD mouse hippocampus and cortex, as well as the behavioral performance of the animals with the Morris Water Maze. RESULTS: One hour of epidural GES delivered over a month significantly (1) reduced Aß load in the AD brain, (2) increased microglia cell counts, decreased cell body size, increased length of cellular processes of the Iba1 + cells, and (3) improved behavioral performance (learning & memory). All these effects were most pronounced when a higher stimulation current was applied. CONCLUSION: The efficacy of GES on the reduction of AD pathology and the intensity-dependent feature provide guidance for the development of this promising therapeutic approach.

5.
Mol Cancer ; 22(1): 121, 2023 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-37516849

RESUMEN

Interleukin-2 (IL-2) and its receptor (IL-2R) are essential in orchestrating immune responses. Their function and expression in the tumor microenvironment make them attractive targets for immunotherapy, leading to the development of IL-2/IL-2R-targeted therapeutic strategies. However, the dynamic interplay between IL-2/IL-2R and various immune cells and their dual roles in promoting immune activation and tolerance presents a complex landscape for clinical exploitation. This review discusses the pivotal roles of IL-2 and IL-2R in tumorigenesis, shedding light on their potential as diagnostic and prognostic markers and their therapeutic manipulation in cancer. It underlines the necessity to balance the anti-tumor activity with regulatory T-cell expansion and evaluates strategies such as dose optimization and selective targeting for enhanced therapeutic effectiveness. The article explores recent advancements in the field, including developing genetically engineered IL-2 variants, combining IL-2/IL-2R-targeted therapies with other cancer treatments, and the potential benefits of a multidimensional approach integrating molecular profiling, immunological analyses, and clinical data. The review concludes that a deeper understanding of IL-2/IL-2R interactions within the tumor microenvironment is crucial for realizing the full potential of IL-2-based therapies, heralding the promise of improved outcomes for cancer patients.


Asunto(s)
Interleucina-2 , Neoplasias , Humanos , Interleucina-2/genética , Interleucina-2/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Carcinogénesis , Inmunoterapia , Ciclo Celular , Microambiente Tumoral
6.
Respir Res ; 24(1): 122, 2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37131252

RESUMEN

BACKGROUD: The role of epigenetic modifications in tumorigenesis has been widely reported. However, the role and mechanism of H3K4me3 modification in lung adenocarcinoma (LUAD) are rarely reported systematically. We, therefore, sought to analyze the characteristics of LUAD associated with H3K4me3 modification, build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD and clarify the potential value of H3K4me3 in immunotherapy of LUAD. METHODS: We evaluated H3K4me3-lncRNA patterns and H3K4me3-lncRNA scores of 477 LUAD samples based on 53 lncRNAs closely correlated to H3K4me3 regulators and comprehensive analyzed the role of these patterns in tumorigenesis and tumor immunity. Using Gene set variation analysis (GSVA), we systematically evaluated the H3K4me3 level of every sample and deeply analyzed the effect of H3K4me3 on the prognosis of LUAD. In addition, we included two independent immunotherapy cohorts to study the impact of high H3K4me3 score on the prognosis of patients. We also used an independent cohort with 52 matched paraffin specimens of LUAD to verify the impact of high H3K3me3 expression on the prognosis of patients. RESULTS: We identified three H3K4me3-lncRNA patterns that exhibited specific immune characteristics. Characterized by immunosuppressive and increased TGFß-mediated epithelial-mesenchymal transition (EMT), patients with high H3K4me3-lncRNA score had a poor overall survival and decreased H3K4me3 score. H3K4me3 score was significantly positively correlated with CD4+T-cell and CD8+T-cell activation, programmed cell death and immune checkpoints (ICs) expression, and was negatively correlated with MYC pathway, TP53 pathway, and cell proliferation. Patients with high H3K4me3 score showed elevated expression of ICs, potentiated CD4 T-cell and CD8 T-cell activation, increased programmed cell death, and suppressed cell proliferation and TGFß-mediated EMT. Patients with high H3K4me3 score and high expression of CTLA4, ICOS, TIGIT, PDCD1LG2, IDO1, CD274, PDCD1, LAG3, or HAVCR2 had the best survival advantage. Two independent immunotherapy cohorts verified that patients with high H3K4me3 score showed an increased inflamed tumor microenvironment (TME) phenotype and enhanced anti-PD-1/L1 immunotherapy response. Immunohistochemistry (IHC) data from 52 matched paraffin specimens of LUAD confirmed that the protein level of H3K4me3 in tumor was significantly lower than that of paracancerous tissues and H3K4me3 brought significant survival benefits to patients with LUAD. CONCLUSIONS: We build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD. More importantly, this study revealed characteristics of H3K4me3 modification in LUAD and clarified the important potential role of H3K4me3 on tumor immunotherapy and patients' survival.


Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Parafina , Carcinogénesis , Pulmón , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética
7.
Med ; 4(1): 10-12, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36640752

RESUMEN

The AP-1 family member BATF maintains immune cell function. Two recent papers by Zhang et al.1 and Itahashi et al.2 investigated the role of this protein in cancer immunity, finding that its depletion in CAR-T cells augments anti-tumor activity and it contributes to Treg-mediated immunosuppression in the tumor microenvironment.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Neoplasias , Humanos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Neoplasias/terapia , Microambiente Tumoral
8.
J Int Med Res ; 50(11): 3000605221134472, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36440806

RESUMEN

OBJECTIVE: To evaluate the feasibility, safety, and short-term outcomes of middle rectal resection followed by transanal specimen extraction. METHODS: Forty-four patients with small mid-rectal tumors underwent laparoscopic rectal resection followed by transanal specimen extraction. RESULTS: The procedure was successful in all patients without intraoperative conversion or additional access. The mean operation time was 182.7 minutes (range, 130-255 minutes), the mean blood loss was 26.5 mL (range, 5-120 mL), the mean postoperative exhaust time was 31.3 hours (range, 16-60 hours), and the mean length of hospital stay was 9.5 days (range, 8-19 days). One patient developed anastomotic leakage, which was treated by intravenous antibiotics and daily pelvic cavity flushes through the abdominal drainage tube. No infection-related complications or anal incontinence were observed. The mean tumor size was 2.1 cm (range, 1.6-3.2 cm), the mean number of harvested lymph nodes was 16.5 (range, 6-31), and the mean follow-up time was 8.5 months (range, 2-16 months). By the last follow-up, no signs of recurrence had been found in any patient. CONCLUSION: The combination of standard laparoscopic proctectomy and transanal specimen extraction could become a well-established strategy for selected patients.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Cirujanos , Humanos , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos
9.
Ann Transl Med ; 10(16): 904, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36111056

RESUMEN

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

10.
J Obstet Gynaecol ; 42(8): 3441-3449, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36757337

RESUMEN

Ovarian cancer (OC) is one of the leading causes of gynaecological cancer mortality in women worldwide. If detected at an early stage (I, II), OC has a 90% 5-year survival rate; nevertheless, symptoms are often hidden, leading to late-stage (III, IV) diagnosis and a poor prognosis. The current diagnostic procedures, such as a pelvic exam, transvaginal ultrasound, CA-125 blood tests, serum HE4 tests and multivariate index assays (MIA), are insufficient. Sadly, surgery is frequently required to confirm a positive diagnosis. Therefore, there has been an increased interest in different biomarkers using a non-invasive test as a tool for the earlier diagnosis of OC to resolve the need for precise and non-invasive diagnostic methods. This review article aims to investigate how biomarkers influence early OC detection and to emphasise the role of using a combination of serum biomarkers panel rather than a single biomarker. In addition, this review provides insights into the current serum biomarkers, urine biomarkers and other emerging biomarkers in the early detection of OC for better specificity and sensitivity and to improve the overall survival (OS) rate.


Asunto(s)
Biomarcadores de Tumor , Antígeno Ca-125 , Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Femenino , Humanos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/orina , Antígeno Ca-125/sangre , Carcinoma , Detección Precoz del Cáncer , Neoplasias Ováricas/diagnóstico
11.
Eur J Surg Oncol ; 46(10 Pt B): e55-e61, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32782201

RESUMEN

BACKGROUND: The aim of this study was to evaluate the safety of natural orifice specimen extraction surgery (NOSES) and to compare the short- and long-term outcomes of three techniques of NOSES for rectal cancer (RC). MATERIALS AND METHODS: A consecutive series of RC patients in stage I-III who underwent laparoscopic NOSES were enrolled. Three main techniques of NOSES included specimen eversion and extra-abdominal resection (EVER), specimen extraction and extra-abdominal resection (EXER) and intra-abdominal resection and specimen extraction (IREX). The postoperative complications, 5-year disease free survival (DFS), 5-year local recurrence rate (LRR) and 5-year distant metastasis rate (DMR) were compared in three techniques. RESULTS: 268 RC patients met inclusion criteria, including 83 patients treated with EVER, 75 patients treated with EXER and 110 patients treated with IREX. Tumor location was the most critical factor associated with technique selection, with P < 0.001. Postoperative complication rate was 12.3% for all patients, and it was 18.1% for EVER, 13.3% for EXER and 7.3% for IREX. There were no significant differences for anastomotic leakage, anastomotic bleeding and intraabdominal abscess among three technique groups, with P > 0.05. For long-term outcomes, the 5-year DFS, 5-year LRR and 5-year DMR were 85.03%, 4.22% and 11.00% for all patients. Patients in advanced tumor stage have worse long-term survival compared with patients in early stage, but no significant survival differences were observed among three technique groups. CONCLUSION: Three techniques of NOSES for RC had acceptable short- and long-term outcomes, and tumor location was a determinant of technique selection.


Asunto(s)
Adenocarcinoma/cirugía , Laparoscopía/métodos , Proctectomía/métodos , Neoplasias del Recto/cirugía , Cirugía Endoscópica Transanal/métodos , Adenocarcinoma/patología , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Supervivencia sin Enfermedad , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Escisión del Ganglio Linfático , Masculino , Mesenterio/cirugía , Persona de Mediana Edad , Mortalidad , Invasividad Neoplásica , Estadificación de Neoplasias , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Neoplasias del Recto/patología , Reoperación/estadística & datos numéricos
12.
J Community Hosp Intern Med Perspect ; 10(4): 328-333, 2020 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-32850090

RESUMEN

BACKGROUND: Leadless pacemakers (LPM) are introduced in cardiovascular market with a goal to avoid lead- and pocket-associated complications due to conventional artificial pacemakers (CPM). The comparison of LPM and CPM complications is not well studied at a case by case level. METHODS: Comprehensive literature was searched on multiple databases performed from inception to December 2019 and revealed 204 cases that received LPM with a comparison of CPM. The data of complications were extracted, screened by independent authors and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.). RESULTS: The complications of CPM were high in comparison to LPM in terms of electrode dislodgement (56% vs 7% of cases, p-value < .0001), pocket site infection rate (16% vs 3.4%, p-value = 0.02), and a lead fracture rate (8% vs 0%, p-value = 0.04). LPMs had a statistically non-significant two-times high risk of pericardial effusion (8%) compared to CPMs (4%) with a p-value = 0.8. CONCLUSION: LPMs appear to have a better safety profile than CPMs. There was a low pocket site and lead-related infections in LPM as compared to CPM. However, LPM can have twice the risk of pericardial effusion than CPMs, but this was not statistically significant.

13.
Exp Ther Med ; 17(1): 260-272, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30651791

RESUMEN

MicroRNAs (miRNAs or miRs) are reported to be dysregulated in the progression and invasion of various human cancer types, including colorectal cancer (CRC). They are also reported to be molecular biomarkers and therapeutic targets in CRC. miRNAs serve functions in a plethora of biological processes, including proliferation, migration, invasion and apoptosis, and several miRNAs have been demonstrated to be involved in CRC carcinogenesis, invasion and metastasis. Aberrant miR-30d expression and its effects have been reported in certain cancer types. However, the function and underlying mechanism of miR-30d in the progression of CRC remains largely unknown. In the current study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify miR-30d expression in CRC tissues. In vivo and in vitro functional assays indicated that miR-30d inhibits CRC cell proliferation. Target prediction online software packages, miRBase, TargetScan and miRANDA, and luciferase reporter assays were used to confirm the target gene GNA13. Specimens from 45 patients with CRC were analyzed for correlation between the expression of miR-30d and the expression of target gene GNA13, evaluated by RT-qPCR. miR-30d was downregulated in CRC tissues and cell lines. Ectopic expression of miR-30d inhibited cell proliferation and invasion and tumor growth ability. By contrast, inhibition of endogenous miR-30d promoted cell proliferation and tumor growth ability of CRC cells. It was indicated that miR-30d directly targets the 3'-untranslated region of the GNA13 gene. Downregulation of miR-30d led to the activation of cell proliferation in CRC. In addition, miR-30d expression was negatively correlated with the expression of GNA13 in CRC tissues. In conclusion, miR-30d inhibits cancer initiation, proliferation and invasion in colorectal cancer via targeting GNA13.

15.
Mol Cancer Ther ; 14(4): 1066-74, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25637315

RESUMEN

Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis. Because of lack of relevant analysis on CAG repeat length and AR expression in colorectal cancer, we aimed to investigate the prognostic value of polymorphic CAG and protein expression of the AR gene in patients with colorectal cancer. A case-control study was carried out on 550 patients with colorectal cancer and 540 healthy controls to investigate whether polymorphic CAG within the AR gene is linked to increased risk for colorectal cancer. Polymorphic CAG and AR expression were analyzed to clarify their relationship with clinicopathologic and prognostic factors in patients with colorectal cancer. The study showed that the AR gene in patients with colorectal cancer had a longer CAG repeat sequence than those in the control group, as well as increased risk for colorectal cancer among females (P = 0.013), males (P = 0.002), and total colorectal cancer population (P < 0.001), respectively. AR expression exhibited a significant difference in long CAG repeat sequence among males (P < 0.001), females (P < 0.001), and total colorectal cancer study population (P < 0.001). Both long CAG repeat sequence and negative AR expression were associated with a short 5-year overall survival (OS) rate in colorectal cancer. Long CAG repeat sequences and the absence of AR expression were closely related to the development of colorectal cancer. Both long CAG and decreased AR expression were correlated with the poor 5-year OS in patients with colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Polimorfismo Genético , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Repeticiones de Trinucleótidos , Adulto , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Expansión de Repetición de Trinucleótido , Carga Tumoral
16.
Mol Cell Biol ; 35(6): 988-1000, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25582198

RESUMEN

MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment.


Asunto(s)
Carcinogénesis/genética , Neoplasias Colorrectales/genética , Proteínas Sustrato del Receptor de Insulina/genética , MicroARNs/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Regulación hacia Abajo/genética , Femenino , Genes Supresores de Tumor , Células HCT116 , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/genética
17.
World J Gastroenterol ; 20(45): 17011-9, 2014 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-25493013

RESUMEN

Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients' outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , MicroARNs/genética , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Regulación Neoplásica de la Expresión Génica , Pruebas Genéticas/métodos , Terapia Genética/métodos , Humanos , MicroARNs/metabolismo , MicroARNs/uso terapéutico , Metástasis de la Neoplasia , Valor Predictivo de las Pruebas
18.
World J Surg Oncol ; 12: 306, 2014 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-25287418

RESUMEN

BACKGROUND: The purpose of this study was to compare short-term clinical outcomes of ileocolonic functional end-to-end anastomosis (FEEA) and end-to-side anastomosis (ESA) following resection of the right colon for cancer. METHODS: We enrolled 379 patients who underwent ileocolonic anastomosis following resection of the right colon for cancer by a single surgeon, from January 2009 through June 2012. Patient characteristics, operative results, and postoperative complications were analyzed. RESULTS: A total of 164 patients received ESA and 215 patients received FEEA. The FEEA group had a lower incidence of anastomotic error (0.9% versus 4.3%; P = 0.04) and a shorter operating time (140.4 ± 14.9 min versus 150.5 ± 20.1 min; P = 0.001). The length of hospital stay (10.9 ± 3.5 days versus 11.3 ± 4.0 days; P = 0.36) and anastomotic leakage (1.8% versus 0.5%; P = 0.20) were similar in both groups. No relevant differences between FEEA and ESA were observed for blood loss, retrieved lymph nodes, first flatus and postoperative complications. CONCLUSION: An FEEA after right hemicolectomy for colon cancer is a safe and reliable anastomotic technique, resulting in a favorable outcome in selected patients with the right colon cancer.


Asunto(s)
Anastomosis Quirúrgica/efectos adversos , Colectomía/efectos adversos , Neoplasias del Colon/cirugía , Tiempo de Internación/estadística & datos numéricos , Complicaciones Posoperatorias/etiología , Fuga Anastomótica/etiología , Neoplasias del Colon/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos
19.
PLoS One ; 9(6): e98455, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24896096

RESUMEN

BACKGROUND: 5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs. Nanoparticle drug delivery vehicles offer superiority over target effect enhancement and abatement of side effects. Little is known however as to the specific effect of nanoparticle on peritoneal dissemination of colon cancer. The aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and investigate the characteristic of NPs and the role of it in peritoneal metastasis nodules formation of human colon cancer. METHODOLOGY/PRINCIPAL FINDINGS: Prepared the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the method of double emulsion. Then evaluate the characteristics of the NPs by scanning electron microscopy, analyzing the particle diameter distribution and determining the loading efficiency. Detect the release features of NPs in vitro and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and mesenterium and survey the size of them. We got NPs with average-diameter of 310 nm. In vitro release test shows NPs can release equably for 5 days with release rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU longer than it in solution group. The number of peritoneal dissemination nodule below 1 mm in 5-FU-sol group(17.3 ± 3.5) and 5-FU-NP group(15.2 ± 3.2) is less than control group(27.2 ± 4.7)(P<0.05). The total number of nodules in 5-FU-NP group(28.7 ± 4.2) is significantly smaller than in 5-FU-sol group(37.7 ± 6.3) (P<0.05). CONCLUSIONS/SIGNIFICANCE: The novel anti-tumor nanoparticles loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory action to peritoneal dissemination of colon cancer in mice.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Fluorouracilo/uso terapéutico , Nanopartículas/química , Neoplasias Peritoneales/tratamiento farmacológico , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/farmacocinética , Línea Celular Tumoral , Neoplasias del Colon/patología , Fluorouracilo/administración & dosificación , Fluorouracilo/farmacocinética , Humanos , Ratones , Ratones Desnudos , Tamaño de la Partícula , Neoplasias Peritoneales/secundario
20.
PLoS One ; 8(12): e81005, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24312514

RESUMEN

BACKGROUND AND OBJECTIVES: Although there was growing evidence supporting the hypothesis that Notch1 was one of the few candidate genes linked with colorectal cancer (CRC) susceptibility, the precise level of Notch1 protein expression in benign and malignant colorectal diseases was still unknown. Our study has investigated the Notch1 expression in benign and malignant colorectal diseases as well as to investigate the role and clinicopathological significance of aberrant expression of Notch1 in CRC. METHODS: The protein expression of Notch1 was examined by immunohistochemistry in 901 clinical specimens with colorectal diseases, including 220 patients with ulcerative colitis, 232 patients with colorectal adenoma and 449 patients with colorectal cancer. Associations between the expression of Notch1 and various clinicopathological features, as well as survival status, were studied. RESULTS: Cytoplasmic Notch1 was expressed in 7.7% of patients with ulcerative colitis, 14.7% of patients with colorectal adenoma and 58.0% of patients with colorectal cancer, respectively. Colorectal cancer patients with high expression levels of Notch1 showed lower overall survival (OS) and disease-free survival (DFS) rates than those patients with low Notch1 expression. CONCLUSIONS: Expression level of Notch1 was gradually increased from precancerous lesions to cancer. It might play as an oncogene in the CRC development, and might be potentially used as a biomarker for prognosis of CRCs.


Asunto(s)
Adenoma , Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Gingivitis Ulcerosa Necrotizante , Proteínas de Neoplasias/biosíntesis , Receptor Notch1/biosíntesis , Adenoma/metabolismo , Adenoma/mortalidad , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Gingivitis Ulcerosa Necrotizante/metabolismo , Gingivitis Ulcerosa Necrotizante/mortalidad , Gingivitis Ulcerosa Necrotizante/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia
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