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BACKGROUND: Previous studies have demonstrated that the expression of homeobox8 (HOXB8) is higher in colorectal cancer (CRC) tissues than in normal tissues; however, the precise role of HOXB8 in human CRC cells remains to be elucidated. METHODS: We generated lentiviral constructs to overexpress and silence HOXB8 in CRC cell lines, and examined their biological functions through MTT, wound healing, colony and transwell, expression of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) related factors through western-blot. RESULTS: HOXB8 knockdown inhibited cellular proliferation and invasion in vitro as well as carcinogenesis and metastasis in vivo. HOXB8 also induced EMT, which is characterized by the down-regulation of E-cadherin and the up-regulation of Vimentin, N-cadherin, Twist, Zeb1 and Zeb2. Moreover, HOXB8 activated STAT3, which is known to play an oncogenic role in diverse human malignancies. CONCLUSIONS: Our results indicate that HOXB8 may be an independent prognostic factor in CRC. Therefore, deserved a deeper research.
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BACKGROUND: Whether the prognoses of different pathological subtypes of colorectal cancer (CRC) at different stages are distinct is unclear. METHODS: We extracted data on all cases of CRC from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The incidence of different pathological subtypes, clinical characteristics, and five-year overall survival (OS) and cause-specific survival (CSS) were analyzed. RESULTS: A total of 384,996 cases diagnosed as adenocarcinoma (AC), mucinous adenocarcinoma (MAC), and signet ring cell carcinoma (SRCC) were included in this analysis. Compared with AC, MAC and SRCC were more likely to reach T4, N2, M1, stages III and IV, and grades III and IV, and patients were generally of a younger age (P < 0.001). Compared with those with AC, patients with MAC and SRCC showed poorer OS (50.6 and 26.8% vs. 60.2%, P < .001), with corresponding HR values of 1.238 (95% CI, 1.213-1.263, P < .001) and 1.592 (95% CI, 1.558-1.627, P < .001), respectively. The MAC and SRCC groups also showed poorer overall CCS (60.9 and 32.5% vs. 67.8%, P < .001), with corresponding HR values of 1.271 (95% CI, 1.242-1.302, P < .001) and 1.724 (95% CI, 1.685-1.765, P < .001), respectively. Compared with patients with AC, those with MAC showed poor OS at every stage and poor CSS at every stage except stage II (P < .05), while patients with SRCC revealed poor OS and CSS at every stage except stage 0 (P < .05). CONCLUSIONS: Patients of different pathological subtypes minimally differed at early stages. However, patients with AC have significantly better prognoses in advanced CRC (stages III and IV) than those with MAC or SRCC. Distinct treatment strategies should be applied depending on a particular histological subtype in advanced CRC.
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Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma/mortalidad , Carcinoma de Células en Anillo de Sello/mortalidad , Neoplasias Colorrectales/mortalidad , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Carcinoma de Células en Anillo de Sello/patología , Causas de Muerte , Estudios de Cohortes , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND There has been no research on the mechanism of HOXB8 action on colorectal cancer so far. This study was designed to investigate the mechanism of HOXB8 regulating colorectal cancer cell proliferation and invasion in vivo and in vitro. MATERIAL AND METHODS HOXB8 shRNA, HOXB8 overexpression, and negative control vector were designed and stably transfected into HCT116 cells. MTT assays were performed to detect cell proliferation. Western blot was utilized to detect HOXB8 expression level in HCT116 stable cells. The invasive and migration abilities were detected by Transwell assay and wound-healing assay. RESULTS HOXB8 knockdown inhibited cell proliferation. The invasiveness of HCT116 cells was significantly reduced following HOXB8 depletion compared with that in the shRNA control group, whereby the rates were reduced by 67% in HOXB8 knockdown group. The wound-healing rate of HOXB8 over-expression cells was significantly increased comparing with that of cells in the blank control group (P<0.05). HOXB8 knockdown promotes apoptosis of HCT116 cells. The expression of E-cadherin was restrained in the HOXB8 over-expression group and increased in the HOXB8 knockdown group. CONCLUSIONS Knock-down of HOXB8 prohibits the proliferation and migration of colorectal cancer cells via the Wnt/ß-catenin signaling pathway and the downregulation of various factors, such as MMP2, c-Myc, CyclinD1,and vimentin. Our data suggested that HOXB8 has great potential to be developed as a novel therapeutic agent for the treatment of human colorectal cancer.
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Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proteínas de Homeodominio/metabolismo , Vía de Señalización Wnt , Animales , Antígenos CD/biosíntesis , Antígenos CD/metabolismo , Cadherinas/biosíntesis , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Transición Epitelial-Mesenquimal , Técnicas de Silenciamiento del Gen , Células HCT116 , Células HEK293 , Xenoinjertos , Proteínas de Homeodominio/biosíntesis , Proteínas de Homeodominio/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , beta Catenina/metabolismoRESUMEN
Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/genética , ARN/biosíntesis , Anciano , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , ARN/genética , ARN CircularRESUMEN
Platinum-based neoadjuvant therapy represented by cisplatin is widely employed in treating Triple-Negative Breast Cancer (TNBC), a particularly aggressive subtype of breast cancer. Nevertheless, the emergence of cisplatin resistance presents a formidable challenge to clinical chemotherapy efficacy. Herein, we revealed the critical role of tumor microenvironment (TME) derived exosomal miR-3960 and phosphorylation at the S16 site of PIMREG in activating NF-κB signaling pathway and promoting cisplatin resistance of TNBC. Detailed regulatory mechanisms revealed that SOD1-upregulated fibroblasts secrete miR-3960 and are then transported into TNBC cells via exosomes. Within TNBC cells, miR-3960 targets and inhibits the expression of BRSK2, an AMPK protein kinase family member. Furthermore, we emphasized that BRSK2 contributes to ubiquitination degradation of PIMREG and modulates subsequent activation of the NF-κB signaling pathway by mediating PIMREG phosphorylation at the S16 site, ultimately affects the cisplatin resistance of TNBC. In conclusion, our research demonstrated the crucial role of SOD1high fibroblast, exosomal miR-3960 and S16 site phosphorylated PIMREG in regulating the NF-κB signaling pathway and cisplatin resistance of TNBC. These findings provided significant potential as biomarkers for accurately diagnosing cisplatin-resistant TNBC patients and guiding chemotherapy strategy selection.
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Cisplatino , Resistencia a Antineoplásicos , Exosomas , MicroARNs , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , Exosomas/metabolismo , Exosomas/genética , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , FN-kappa B/genética , Fosforilación , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente TumoralRESUMEN
AIM: To measure global gene expression in primary advanced colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy. MATERIALS & METHODS: Samples from primary advanced colorectal cancer patients were collected. The effects of chemotherapy were evaluated, and patients were divided into an experimental group and a control group. Cancerous tissue gene expression profiles were detected by chip technology. Valuable biomarkers were screened by bioinformatic analysis. Immunohistochemical analysis was performed to characterize the pattern of HOXB8 and KLK11 expression. HOXB8 and KLK11 signal probe values were analyzed using receiver operating characteristic analysis. RESULTS: There were differentially expressed genes in the two groups. HOXB8 and KLK11 proteins were observed in the nucleus and on the outside of the cancer cells, respectively. Their prediction accuracies were 79.9 and 76.7%, respectively. CONCLUSION: HOXB8 and KLK11 may be classified as valuable biomarkers, as they can predict the effects of FOLFOX4 chemotherapy in primary advanced colorectal cancer patients.
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Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Proteínas de Homeodominio/genética , Serina Endopeptidasas/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores Farmacológicos , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Pronóstico , Resultado del TratamientoRESUMEN
Background: Metastases at regional lymph nodes could easily occur in patients with high-histological-grade colorectal cancer (CRC). However, few models were built on the basis of lymph nodes to predict the outcome of patients with histological grades III-IV CRC. Methods: Data in the Surveillance, Epidemiology, and End Results databases were used. Univariate and multivariate analyses were performed. A personalized prediction model was built in accordance with the results of the analyses. A nomogram was tested in two datasets and assessed using a calibration curve, a consistency index (C-index), and an area under the curve (AUC). Results: A total of 14,039 cases were obtained from the database. They were separated into two groups (9828 cases for constructing the model and 4211 cases for validation). Logistic and Cox regression analyses were then conducted. Factors such as log odds of positive lymph nodes (LODDS) were utilized. Then, a personalized prediction model was established. The C-index in the construction and validation groups was 0.770. The 1-, 3-, and 5-year AUCs were 0793, 0.828, and 0.830 in the construction group, respectively, and 0.796, 0.833, and 0.832 in the validation group, respectively. The calibration curves showed well consistency in the 1-, 3- and 5-year OS between prediction and reality in both groups. Conclusion: The nomogram built based on LODDS exhibited considerable reliability and accuracy.
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INTRODUCTION: Lymphovascular invasion (LVI) is a micropathological tumor factor believed to increase the risk of tumor metastasis and spread. Propensity score matching (PSM) is a statistical method that can control confounding factors. Current research rarely considers the confounding relationship between LVI and other factors that may influence prognosis. This study aimed to investigate the relationship between LVI and prognosis in patients with stage I-III colorectal cancer (CRC) by using propensity score matching (PSM). METHODS: This was a retrospective study involving 610 patients. PSM was used to adjust for baseline differences between the groups. The survival rates were calculated. A nomogram was constructed based on the Cox proportional hazards model before matching. The C-index, receiver operating characteristic curve (ROC), and calibration curve were used to evaluate the nomogram. RESULTS: A total of 150 patients tested positive for LVI, accounting for 24.6% of the total, and 120 couples of patients were identified after PSM. The survival curve and Cox proportional hazards model after matching confirmed the adverse effects of LVI on tumor prognosis. The Cox proportional hazards model before matching showed that age, carcinoembryonic antigen level, T stage, N stage, histologic grade and LVI were independent prognostic factors. The C-index of the nomogram established based on the Cox proportional hazards model was 0.787 (95% CI=0.728-0.845). The areas under the curve were 0.796 in the 3-year ROC. CONCLUSIONS: LVI is an adverse prognostic factor in patients with stage I-III colorectal cancer.
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Neoplasias Colorrectales , Humanos , Pronóstico , Estudios Retrospectivos , Estadificación de Neoplasias , Puntaje de Propensión , Neoplasias Colorrectales/patologíaRESUMEN
Colon cancer is a major cause of cancer-related death. Despite recent improvements in the treatment of colon cancer, new strategies to improve the overall survival of patients are urgently needed. Heat shock protein 90 (HSP90) is widely recognized as a promising target for treating various cancers, including colon cancer. However, no HSP90 inhibitor has been approved for clinical use due to limited efficacy. In this study, we evaluated the antitumor activities of HSP90 inhibitors in combination with piperlongumine in colon cancer cells. We show that combination treatment with HSP90 inhibitors and piperlongumine displayed strong synergistic interaction in colon cancer cells. These agents synergize by promoting ER stress, JNK activation, and DNA damage. This process is fueled by oxidative stress, which is caused by the accumulation of reactive oxygen species. These studies nominated piperlongumine as a promising agent for HSP90 inhibitor-based combination therapy against colon cancer.
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Colorectal cancer (CRC) is the third most common cancer, and is one of the leading causes of cancer-related death worldwide. At the time of diagnosis, about 20% of patients with CRC present metastatic disease. Regorafenib, an oral multi-kinase inhibitor, has been demonstrated the efficacy and tolerability in patients with metastatic CRC. Oxaliplatin is a frontline treatment regimen for CRC, and combination treatments with oxaliplatin and other chemotherapeutic agents exert superior therapeutic effects. However, side effects and drug resistance limited their further clinical application. Here, we found that combined treatment with regorafenib and oxaliplatin synergistically enhanced anti-tumor activities in CRC by activating reactive oxygen species (ROS) mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 signaling pathways. Regorafenib promoted ROS production by suppressing the expression of selenoprotein S (SELENOS). Knocking down SELENOS sensitized ROS-mediated anti-tumor effects of regorafenib in CRC cells. Furthermore, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with regorafenib and oxaliplatin. This study provided solid experimental evidences for the combined treatment with regorafenib and oxaliplatin in CRC.
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Neoplasias del Colon , Animales , Ratones , Humanos , Oxaliplatino/farmacología , Especies Reactivas de Oxígeno , Neoplasias del Colon/tratamiento farmacológico , Muerte Celular , Estrés Oxidativo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Since Heald proposed the total mesorectal excision (TME) procedure, the prognosis of patients with rectal cancer has been significantly improved. But Heald did not specifically describe the anterior surgical plane in female patients. And the surgical plane for mobilizing the anterior rectal wall during TME surgery in female patients remains controversial. AIM: To investigate the anatomy of the female pelvis and identify the optimal plane for mobilizing the anterior rectal wall. METHODS: We retrospectively collected surgical procedure videos and clinical data of female patients diagnosed with middle or low rectal cancer who underwent the TME procedure between January 2020 and October 2022 across six hospitals. The patients were divided into two groups based on the surgical approach used to mobilize the anterior rectal wall: The experimental group was to open the peritoneum at the lowest point of the peritonea reflection and enter the plane for mobilizing, while the control group was cut at 0.5-1 cm above the peritoneal reflection and enter another plan. Then, we compared the preoperative and postoperative information between the two groups. We also dissected and observed ten adult female pelvises to analyze the anatomic structure and compare the entry plane between the two approaches. Finally, we researched the pathological structure between the rectum and the vagina. RESULTS: Finally, 77 cases that met the criteria were included in our study. Our observations revealed that the experimental group underwent a smooth procedure, entering the plane amidst the mesorectal fascia and adventitia of the vagina, whereas the control group entered the plane between the vaginal adventitia and muscle layers. Compared to the control group, the experimental group showed a significant decrease in intraoperative bleeding [22.5 (19.5-50) mL vs 17 (5-20) mL, P = 0.01], as well as a shorter duration of hospitalization [9 (7-11.25) d vs 7 (6-10) d, P = 0.03]. Through the examination of surgical videos and cadaveric studies, we discovered that Denonvilliers' fascia is absent in females. Additionally, pathological sections further revealed the absence of Denonvilliers' fascia in females, with only loose connective tissue present between the mesorectal fascia and adventitia of the vagina. CONCLUSION: The plane amidst the mesorectal fascia and vaginal adventitia is the optimal surgical plane to mobilize the anterior rectal wall for female patients undergoing the TME procedure.
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Laparoscopía , Neoplasias del Recto , Adulto , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Recto/cirugía , Recto/patología , Pelvis/anatomía & histología , Pelvis/patología , Peritoneo/patología , Laparoscopía/métodosRESUMEN
Objective: To investigate the interaction between LIMK1 and STK25 and its expression in colon cancer and its effect on the malignant evolution of colon cancer. Methods: Fluorescence quantitative PCR and immunohistochemistry were used to detect the expression of the LIMK1 gene in cancer and adjacent tissues of 20 clinical colon cancer samples. The overexpression plasmids of LIMK1 and STK25 were constructed. An shRNA specific to LIMK1 was synthesized and transfected into colon cancer cell lines. The expression levels of EMT-related markers in cell lines were detected by real-time PCR. The effects of LIMK1 and STK25 on the proliferation and invasion of colon cancer cell lines were detected by CCK-8 assay, Transwell, and clonogenesis. Results: LIMK1 interacted with STK25 and was highly expressed in colon cancer. High expression of LIMK1 and STK25 is associated with poor prognosis in colon cancer patients. LIMK silencing inhibits proliferation, invasion, and EMT of colon cancer. Cotransfection of LIMK1 and STK25 promotes the malignant progression and EMT of colon cancer. Conclusion: Protein interaction between LIMK1 and STK25 occurs. Overexpression of LIMK1 and STK25 plays a role in promoting cell proliferation and invasion in colon cancer tissues and cells. They also play a role in promoting the occurrence and development of colon cancer.
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Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.
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BACKGROUND: Globally, colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Oxaliplatin based treatments are frequently used as chemotherapeutic methods for CRC, however, associated side effects and drug resistance often limit their clinical application. Dihydroartemisinin (DHA) induces apoptosis in various cancer cells by increasing reactive oxygen species (ROS) production. However, the direct target of DHA and underlying molecular mechanisms in oxaliplatin-mediated anti-tumor activities against CRC are unclear. METHODS: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, and colony formation assays to investigate cell phenotype alterations and ROS generation. We also used quantitative Real-Time PCR (qRT-PCR) and western blotting to measure relative gene and protein expression. Finally, an in vivo mouse xenograft model was used to assess the anti-tumor activity of oxaliplatin and DHA alone, and combinations. RESULTS: DHA synergistically enhanced the anti-tumor activity of oxaliplatin in colon cancer cells by regulating ROS-mediated ER stress, signal transducer and activator of transcription 3 (STAT3), C-Jun-amino-terminal kinase (JNK), and p38 signaling pathways. Mechanistically, DHA increased ROS levels by inhibiting peroxiredoxin 2 (PRDX2) expression, and PRDX2 knockdown sensitized DHA-mediated cell growth inhibition and ROS production in CRC cells. A mouse xenograft model showed strong anti-tumor effects from combination treatments when compared with single agents. CONCLUSIONS: We demonstrated an improved therapeutic strategy for CRC patients by combining DHA and oxaliplatin treatments.
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BACKGROUND: Prognoses for treatment of middle and lower rectal cancer remain unclear because anatomical and complex surgical procedures specifically influence long-term outcomes. This study analyzes the long-term outcomes of laparoscopic versus open resection for middle and lower rectal cancer. METHODS: Patients (laparoscopic, n = 113; open, n = 123) who underwent curative resection for middle and lower rectal cancer from 2000 to 2005 participated in the study. All operations were performed by the same surgical team with extensive experience in laparoscopic and open procedures. The mean follow-up time of all patients was 74.8 months. RESULTS: No statistical differences in local recurrence rate (9.1% vs. 6.4%; log-rank = 0.432; p = 0.511) and in distant recurrence rate (19.7% vs. 15.5%; log-rank = 0.505; p = 0.477) between laparoscopic and open groups were observed within 5 years. The 5-year overall survival rates of the laparoscopic and open groups were 77.9 and 78.9%, respectively; no significant statistical difference was observed between them (log-rank = 0.012; p = 0.913). The 5-year survival rates between groups were not different between stages: stage I (91.7% vs. 92.0%; p = 0.950), stage II (82.8% vs. 79.4%; p = 0.643), and stage III (66.7% vs. 70.3%; p = 0.850). However, significant statistical differences between different stages were observed (log-rank = 11.156; p = 0.004). CONCLUSION: Laparoscopic and open surgery for middle and lower rectal cancer offer similar long-term outcomes. The continued use of laparoscopic surgery in these patients can be supported.
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Laparoscopía/métodos , Neoplasias del Recto/cirugía , Distribución de Chi-Cuadrado , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Pronóstico , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/terapia , Estadísticas no Paramétricas , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer related deaths worldwide. Despite recent advancements in surgical and molecular targeted therapies that improved the therapeutic efficacy in CRC, the 5 years survival rate of CRC patients still remains frustratingly poor. Accumulated evidences indicate that microRNAs (miRNAs) play a crucial role in the progression and metastasis of CRC. Dysregulated miRNAs are closely associated with cancerous phenotypes (e.g. enhanced proliferative and invasive ability, evasion of apoptosis, cell cycle aberration, and promotion of angiogenesis) by regulating their target genes. In this review, we provide an updated overview of tumor suppressive and oncogenic miRNAs, circulatory miRNAs, and the possible causes of dysregulated miRNAs in CRC. In addition, we discuss the important functions of miRNAs in drug resistance of CRC.
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Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos , MicroARNs/genética , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis de la Neoplasia , Análisis de SupervivenciaRESUMEN
Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with the miR-196b-5p expression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Interleucina-6/metabolismo , Neoplasias Pulmonares/genética , MicroARNs/genética , Factor de Transcripción STAT3/metabolismo , Receptor fas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/patologíaRESUMEN
Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival. Overexpression of Trx-1 enhanced CRC cell invasion and metastasis in vitro and in vivo. Conversely, suppression of Trx-1 expression decreased cell invasion and metastasis in vitro and in vivo. Moreover, Trx-1 activates S100P gene transcription. S100P, in turn, promotes Trx-1 expression and nuclear localization by upregulating p-ERK1/2 and downregulating TXNIP expression. Our finding provides new insight into the mechanism of Trx-1/S100P axis in the promotion of CRC metastasis, and suggests that the Trx-1/S100P axis and their related signaling pathways could be novel targets for the treatment of metastatic CRC.
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Proteínas de Unión al Calcio/metabolismo , Movimiento Celular , Neoplasias Colorrectales/metabolismo , Proteínas de Neoplasias/metabolismo , Tiorredoxinas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Proteínas de Unión al Calcio/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Retroalimentación Fisiológica , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Fosforilación , Interferencia de ARN , Transducción de Señal , Tiorredoxinas/genética , Factores de Tiempo , Transcripción Genética , Activación Transcripcional , TransfecciónRESUMEN
BACKGROUND: Laparoscopic surgery for middle and lower rectal cancer remain controversial because anatomical and complex surgical procedures specifically influence oncologic outcomes. This study analyzes the long-term outcomes of laparoscopic versus open surgery for middle and lower rectal cancer. METHODS: Patients (laparoscopic: n = 129, open: n = 152) who underwent curative resection for middle and lower rectal cancer from 2003 to 2008 participated in the study. The same surgical team performed all operations. The mean follow up time of all patients was 74.3 months. RESULTS: No statistical difference in local recurrence rate (7.8% vs. 7.2%; log-rank = 0.024; P = 0.876) and distant recurrence rate (20.9% vs.16.4%; log-rank = 0.699; P = 0.403) between laparoscopic and open groups were observed within 5 years. The 5-year overall survival rates of the laparoscopic and open groups were 72.9% and 75.7%, respectively; no significant statistical difference was observed between them (log-rank = 0.163; P = 0.686). The 5-year survival rates between groups were not different between stages: Stage I (92.6% vs. 86.7%; log-rank = 0.533; P = 0.465); stage II (75.8% vs. 80.5%; log-rank = 0.212; P = 0.645); and Stage III (63.8% vs. 69.1%, log-rank = 0272;P = 0.602). However, significant statistical difference amongst different stages were observed (log-rank = 1.802; P = 0.003). CONCLUSION: Laparoscopic and open surgery for middle and lower rectal cancer offer equivalent long-term oncologic outcomes. Laparoscopic surgery is feasible in these patients.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía , Neoplasias del Recto/cirugía , Adulto , Anciano , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapiaRESUMEN
Thermochromic VO2 nanoparticles have been dispersed into polyvinyl pyrrolidone (PVP) fibers by electrospinning of a VO2-PVP blend solution. The structure and optical properties of the obtained composite fiber mat were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet-visible (UV-Vis) spectrophotometry, and Fourier transform infrared (FT-IR) spectroscopy. The fiber mat revealed two diffuse reflectance states in infrared spectral region at temperatures under and above the phase transition temperature of VO2 and its IR reflectance is smaller in high temperature. The difference of diffuse reflectance between the two states (ΔRdif) was obvious to be more than 25% in the wavelengths from 1.5 µm to 6 µm. The diffuse reflectance of the fiber mat could be controlled by adjusting the diameter of the fiber or the content of VO2 in the fibers and this particular optical property was explained by a multiple scattering-absorbing process.