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1.
World J Gastroenterol ; 29(19): 2992-3002, 2023 May 21.
Article in English | MEDLINE | ID: mdl-37274805

ABSTRACT

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.


Subject(s)
Laparoscopy , Rectal Neoplasms , Adult , Humans , Female , Retrospective Studies , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Rectum/surgery , Rectum/pathology , Pelvis/anatomy & histology , Pelvis/pathology , Peritoneum/pathology , Laparoscopy/methods
2.
Front Biosci (Landmark Ed) ; 28(4): 69, 2023 04 06.
Article in English | MEDLINE | ID: mdl-37114536

ABSTRACT

Colorectal cancer (CRC) is one of the high incident and lethal malignant tumors, and most of the patients are diagnosed at an advanced stage. The treatment of CRC mainly includes surgery, chemotherapy, radiotherapy and molecular targeted therapy. Despite these approaches have increased overall survival (OS) of CRC patients, the prognosis of advanced CRC remains poor. In recent years, remarkable breakthroughs have been made in tumor immunotherapy, especially immune checkpoint inhibitors (ICIs) therapy, bringing long-term survival benefits to tumor patients. With the increasing wealth of clinical data, ICIs have achieved significant efficacy in the treatment of high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) advanced CRC, but the therapeutic effects of ICIs on microsatellite stable (MSS) advanced CRC patients is currently unsatisfactory. As increasing numbers of large clinical trials are performed globally, patients treated with ICIs therapy also have immunotherapy-related adverse events and treatment resistance. Therefore, a large number of clinical trials are still needed to evaluate the therapeutic effect and safety of ICIs therapy in advanced CRC. This article will focus on the current research status of ICIs in advanced CRC and discuss the current predicament of ICIs treatment.


Subject(s)
Brain Neoplasms , Colorectal Neoplasms , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Molecular Targeted Therapy
4.
Curr Gene Ther ; 23(5): 356-367, 2023.
Article in English | MEDLINE | ID: mdl-37076469

ABSTRACT

BACKGROUND: Radiotherapy is a standard adjuvant therapy in patients with progressive rectal cancer, but many patients are resistant to radiotherapy, leading to poor prognosis. Our study identified microRNA-652 (miR-652) value on radiotherapy response and outcome in rectal cancer patients. METHODS: miR-652 expression was determined by qPCR in primary rectal cancer from 48 patients with and 53 patients without radiotherapy. The association of miR-652 with biological factors and the prognosis was examined. The biological function of miR-652 was identified through TCGA and GEPIA database searches. Two human colon cancer cell lines (HCT116 p53+/+ and p53-/-) were used for in vitro study. The molecular interactions of miR-652 and tumor suppressor genes were studied through a computational approach. RESULTS: In RT patients, miR-652 expression was significantly decreased in cancers when compared to non-radiotherapy cases (P = 0.002). High miR-652 expression in non-RT patients was with increased apoptosis marker (P = 0.036), ATM (P = 0.010), and DNp73 expression (P = 0.009). High miR-652 expression was related to worse disease-free survival of non-radiotherapy patients, independent of gender, age, tumor stage, and differentiation (P = 0.028; HR = 7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of miR-652 with apoptosis in rectal cancer. miR-652 expression in cancers was negatively related to WRAP53 expression (P = 0.022). After miR-652 inhibition, the estimation of reactive oxygen species, caspase activity, and apoptosis in HCT116 p53+/+ cells was significantly increased compared with HCT116 p53-/- cells after radiation. The results of the molecular docking analysis show that the miR652-CTNNBL1 and miR652-TP53 were highly stable. CONCLUSION: Our findings suggest the potential value of miR-652 expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.


Subject(s)
MicroRNAs , Rectal Neoplasms , Humans , Tumor Suppressor Protein p53/genetics , Sweden , Molecular Docking Simulation , Biomarkers, Tumor , Rectal Neoplasms/genetics , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/pathology , Prognosis , MicroRNAs/genetics
5.
Front Oncol ; 12: 960539, 2022.
Article in English | MEDLINE | ID: mdl-36185219

ABSTRACT

Gastric cancer (GC) is one of the most prevalent malignancies and the most common causes of cancer-related mortality worldwide. Furthermore, the prognosis of advanced GC remains poor even after surgery combined with chemoradiotherapy. As a small group of cells with unlimited differentiation and self-renewal ability in GC, accumulating evidence shows that GC stem cells (GCSCs) are closely associated with the refractory characteristics of GC, such as drug resistance, recurrence, and metastasis. With the extensive development of research on GCSCs, GCSCs seem to be promising therapeutic targets for GC. However, the relationship between GCSCs and GC is profound and intricate, and its mechanism of action is still under exploration. In this review, we elaborate on the source and key concepts of GCSCs, systematically summarize the role of GCSCs in GC and their underlying mechanisms. Finally, we review the latest information available on the treatment of GC by targeting GCSCs. Thus, this article may provide a theoretical basis for the future development of the novel targets based on GCSCs for the treatment of GC.

6.
Front Oncol ; 12: 1054846, 2022.
Article in English | MEDLINE | ID: mdl-36591525

ABSTRACT

Colorectal cancer (CRC) is the most common malignant tumor and one of the most lethal malignant tumors in the world. Despite treatment with a combination of surgery, radiotherapy, and/or systemic treatment, including chemotherapy and targeted therapy, the prognosis of patients with advanced CRC remains poor. Therefore, there is an urgent need to explore novel therapeutic strategies and targets for the treatment of CRC. MicroRNAs (miRNAs/miRs) are a class of short noncoding RNAs (approximately 22 nucleotides) involved in posttranscriptional gene expression regulation. The dysregulation of its expression is recognized as a key regulator related to the development, progression and metastasis of CRC. In recent years, a number of miRNAs have been identified as regulators of drug resistance in CRC, and some have gained attention as potential targets to overcome the drug resistance of CRC. In this review, we introduce the miRNAs and the diverse mechanisms of miRNAs in CRC and summarize the potential targeted therapies of CRC based on the miRNAs.

7.
World J Clin Cases ; 9(16): 3858-3868, 2021 Jun 06.
Article in English | MEDLINE | ID: mdl-34141742

ABSTRACT

BACKGROUND: Gastrointestinal involvement in Behçet's disease (GIBD) and Crohn's disease (CD) are inflammatory diseases sharing a considerable number of similarities. However, different from CD, the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines. AIM: To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD. METHODS: We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University. A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited. Information including demographic data, medication, and operative and postoperative parameters were collected and analyzed. As the incidence of surgical GIBD is low, their detailed medical records were reviewed and compared to previous studies. Moreover, the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents. RESULTS: Indication for first surgery was often acute intestinal perforation for GIBD patients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P = 0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CD patients. Approximately 40% of patients with GIBD and 23.6% of patients with CD developed postoperative complications, 50% of patients with GIBD and 38.7% of patients with CD had recurrence postoperatively, and 40% (4/10) of patients with GIBD and 26.4% (28/106) of patients with CD underwent reoperations. The average period of postoperative recurrence was 7.87 mo in patients with Behçet's disease (BD) and 10.43 mo in patients with CD, whereas the mean duration from first surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CD patients. Surgical patients with GIBD more often used corticosteroids (6/10 vs 7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively, whereas surgical patients with CD often used infliximab (27/106), azathioprine, or 6-mercaptopurine (74/106) for maintenance therapy. CONCLUSION: Patients suffering GIBD require surgery mostly under emergency situations, which may be more susceptible to recurrence and reoperation and need more aggressive postoperative treatment than patients with CD.

8.
Front Oncol ; 11: 803974, 2021.
Article in English | MEDLINE | ID: mdl-35047411

ABSTRACT

Gastric cancer (GC) remains one of the leading causes of cancer-related death worldwide. Cancer stem cells (CSCs) might be responsible for tumor initiation, relapse, metastasis and treatment resistance of GC. The tumor microenvironment (TME) comprises tumor cells, immune cells, stromal cells and other extracellular components, which plays a pivotal role in tumor progression and therapy resistance. The properties of CSCs are regulated by cells and extracellular matrix components of the TME in some unique manners. This review will summarize current literature regarding the effects of CSCs and TME on the progression and therapy resistance of GC, while emphasizing the potential for developing successful anti-tumor therapy based on targeting the TME and CSCs.

9.
Front Oncol ; 10: 567042, 2020.
Article in English | MEDLINE | ID: mdl-33123477

ABSTRACT

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P = 0.042) and non-RT patients (P = 0.003) and was associated with mucinous histological type (P = 0.004), COX-2 (P = 0.042), and p73 expression (P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P = 0.033) and with WRAP53 expression (P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P = 0.015), AEG-1 (astrocyte elevated gene-1) (P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.

10.
Article in English | MEDLINE | ID: mdl-32370729

ABSTRACT

Colorectal cancer (CRC) is one of the most common cancers and a significant cause of tumor- related deaths worldwide. Traditional biomarkers, such as CEA and CA199, are not sensitive enough to provide useful information for early diagnosis and treatment and are rather used to track the clinical progression of the disease. There is growing evidence that microRNAs (miRNA) are potentially superior to traditional biomarkers as promising non-invasive biomarkers for the timely diagnosis and prediction of prognosis or treatment response in the management of CRC. In this review, the latest studies on the dysregulation of miRNAs expression in CRC and the potential for miRNAs to serve as biomarkers were collected. Given the limitations of miRNA, as discussed in this paper, its clinical applications as a diagnostic biomarker should be limited to use in combination with other biomarkers. Further research is necessary to elucidate the clinical applications of miRNA in therapy for CRC.


Subject(s)
Biomarkers, Tumor/biosynthesis , Colorectal Neoplasms/metabolism , MicroRNAs/biosynthesis , Animals , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/genetics , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/physiology , Early Detection of Cancer/methods , Genetic Therapy/methods , Genetic Therapy/trends , Humans , MicroRNAs/genetics , Rectal Neoplasms/genetics , Rectal Neoplasms/metabolism , Rectal Neoplasms/therapy
11.
J Oncol ; 2019: 5689464, 2019.
Article in English | MEDLINE | ID: mdl-30800162

ABSTRACT

CD200 imparts an immunoregulatory signal through its receptor, CD200R1, leading to the suppression of tumor specific immunity. The mechanism of CD200:CD200R1 signaling pathway is still uncertain. Our aim was to investigate the expression and localization of CD200 and its receptor CD200R1 and their clinical significance in rectal cancer patients. We examined the immunohistochemical expressions and localizations of CD200 and CD200R1 in 140 rectal cancer patients. Among the patients, 79 underwent the preoperative radiotherapy and the others were untreated prior to the surgery. In addition, 121 matched normal rectal mucosa samples were evaluated. The results of immunohistochemical analysis showed a strikingly high level of CD200 in tumor cells (p=0.001) and CD200R1 expression in normal mucosal epithelium and stromal cells. Importantly, CD200R1 was overexpressed in stromal cells of the metastatic cancer patients compared to patients without metastases (p=0.002). More than that, 87% of metastatic patients had a phenotype of upregulated CD200 in tumor cells accompanied by overexpressed CD200R1 in stromal cells. In addition, low levels of CD200 were correlated with improved overall survival in untreated patients. We showed that tumor-stroma communication through CD200 and its receptor interaction is selected in patients with high risk of relapse. High levels of these molecules support instigation of the far and local metastatic nest that provides solid ground for metastasis. Our current data also disclose a mechanism by which CD200:CD200R1 affects tumor progression and may strengthen the feasibility of targeting CD200 or CD200R1 as anticancer strategy.

12.
Sci Rep ; 8(1): 12554, 2018 08 22.
Article in English | MEDLINE | ID: mdl-30135478

ABSTRACT

To evaluate whether aggressive characteristics of rectal cancer can be predicted by the apparent diffusion coefficient (ADC) obtained using readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted magnetic resonance. We enrolled one hundred and fifteen patients. The image quality of ADC maps by rs-EPI was compared with that by traditional single-shot echo-planar imaging (ss-EPI), and ADC measurement was performed on the rs-EPI based ADC maps. Differences in ADC values of tumors grouped according to differentiation grade, clinical T stage and plasmatic carcinoembryonic antigen (CEA) level were tested. The correlation between each aggressive characteristic and the corresponding ADC values was evaluated. The image quality of ADC maps obtained by rs-EPI was superior toss-EPI (P < 0.05). The ADC values of tumor were categorized based on the following differentiation grades: poor (0.89 ± 0.12 × 10-3 mm2/s), moderate (1.13 ± 0.25 × 10-3 mm2/s), and good (1.31 ± 0.19 × 10-3 mm2/s); P < 0.001. Tumors with lower differentiation grades corresponded to lower ADC values (r = 0.59, P < 0.001). However, ADC differences were not observed in different clinical T stage (P = 0.22) and plasmatic CEA level (P = 0.38). Rs-EPI sequence-based ADC values represent a potential imaging marker for the aggressive rectal cancer characteristics.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Echo-Planar Imaging/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Aged , Female , Humans , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Observer Variation
13.
Int J Radiat Biol ; 94(1): 79-87, 2018 01.
Article in English | MEDLINE | ID: mdl-29099643

ABSTRACT

AIM: To demonstrate the radiation responses of tafazzin (TAZ) protein in colon cancer. METHODS: TAZ expression was examined in colon cancer cell lines SW480, KM12C, SW620 and KM12L4a. KM12C and KM12L4a cell lines were used for this experiment with exposure to X- and UV rays (mW/cm2). HCT15 cell line was used to test the expression of TAZ by using an anti-TAZ drug, namely 9-fluorenone, which is a Hippo-YAP/TAZ signaling inhibitor. The experimentation also involved exposing HCT15 cell line, to UV radiation. Cell proliferation and apoptosis studies were carried out. TAZ interactions with oncoproteins were screened and the oncoproteins Livin, MAC30 and FXYD-3 were considered for in silico protein-protein interaction studies. RESULTS: TAZ protein was significantly downregulated after 2 Gy radiations. 9-Fluorenone inhibited the expression of TAZ. Action of 9-fluorenone along with radiation, decreased the percentage of proliferation and increased apoptosis. Computational studies predicted that TAZ interacts with the oncoproteins Livin, MAC30 and FXYD-3. CONCLUSIONS: Our results suggest that TAZ plays a significant role in non-metastatic KM12C cells and is predominantly seen in the colon cancer cells isolated from primary stages of cancer. Thus, use of TAZ protein as a biomarker will be an efficient way to detect tumors in the early stages and treatment may be modulated with radiation before surgery/therapy.


Subject(s)
Colonic Neoplasms/radiotherapy , Transcription Factors/physiology , Acyltransferases , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Down-Regulation , Humans , Molecular Docking Simulation , Transcription Factors/chemistry , Transcription Factors/genetics
14.
Eur J Radiol ; 85(10): 1818-1823, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27666622

ABSTRACT

PURPOSE: To determine whether readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted imaging (DWI) can improve the image quality in patients with rectal cancer compared with single-shot echo-planar imaging (ss-EPI) DWI using 3.0 T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the Institutional Review Board, and informed consent was obtained from all patients. Seventy-one patients with rectal cancer were enrolled in this study. For all patients, both rs-EPI and ss-EPI DWI were performed using a 3T MR scanner. Two radiologists independently assessed the overall image quality, lesion conspicuity, geometric distortion and distinction of anatomical structures. The signal-to-noise ratio (SNR), lesion contrast, contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) were also measured. Comparisons of the quantitative and qualitative parameters between the two sequences were performed using the paired t-test and the Wilcoxon signed rank test. RESULTS: The scores of overall image quality, lesion conspicuity, geometric distortion and distinction of anatomical structures of rs-EPI were all significantly higher than those of ss-EPI (all p<0.05). The SNR and CNR were higher in rs-EPI than those in ss-EPI (all p<0.05). There was no significant difference between ss-EPI and rs-EPI with regard to ROI size and mean ADCs of the tumour (p=0.574 and p=0.479, respectively), but the mean ADC of the normal tissue was higher in rs-EPI than in ss-EPI (1.73±0.30×10(-3)mm(2)/s vs. 1.60±0.31×10(-3)mm(2)/s, p=0.001). CONCLUSIONS: DW imaging based on readout-segmented echo-planar imaging is a clinically useful technique to improve the image quality for the purpose of evaluating lesions in patients with rectal tumours.


Subject(s)
Diffusion Magnetic Resonance Imaging , Echo-Planar Imaging , Image Processing, Computer-Assisted , Rectal Neoplasms/diagnostic imaging , Adult , Aged , Artifacts , Diffusion Magnetic Resonance Imaging/methods , Echo-Planar Imaging/methods , Feasibility Studies , Female , Humans , Image Enhancement , Male , Middle Aged , Observer Variation , Rectal Neoplasms/pathology , Reproducibility of Results , Sensitivity and Specificity , Signal-To-Noise Ratio
15.
Oncotarget ; 6(42): 44758-80, 2015 Dec 29.
Article in English | MEDLINE | ID: mdl-26556872

ABSTRACT

Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan® miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-α, IL-1ß, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1α were increased, and IFN-γ expression was decreased after radiation, whereas, IL-6, IFN-γ, TNF-α, IL-1ß, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1α were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camptothecin/analogs & derivatives , Chemokines/metabolism , Chemoradiotherapy , Colonic Neoplasms/therapy , Cytokines/metabolism , MicroRNAs/metabolism , Tumor Suppressor Protein p53/metabolism , Camptothecin/pharmacology , Chemokines/genetics , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Computational Biology , Cytokines/genetics , Databases, Genetic , Dose-Response Relationship, Drug , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , HCT116 Cells , Heterozygote , Humans , Inhibitory Concentration 50 , Irinotecan , MicroRNAs/genetics , Mutation , Radiation Dosage , Signal Transduction , Time Factors , Transfection , Tumor Suppressor Protein p53/genetics
16.
Cancer Biol Ther ; 16(12): 1738-45, 2015.
Article in English | MEDLINE | ID: mdl-26528635

ABSTRACT

Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasn't been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.


Subject(s)
Matrix Attachment Region Binding Proteins/metabolism , Rectal Neoplasms/metabolism , Rectal Neoplasms/mortality , Biomarkers, Tumor , Cell Line, Tumor , Combined Modality Therapy , Female , Gene Expression , Gene Knockdown Techniques , Humans , Immunohistochemistry , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Matrix Attachment Region Binding Proteins/genetics , Models, Biological , Neoplasm Metastasis , Patient Outcome Assessment , Prognosis , Radiation Tolerance/genetics , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Recurrence
17.
Medicine (Baltimore) ; 94(32): e1297, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26266366

ABSTRACT

The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P = 0.012), coexistence of adenoma (P = 0.012), microsatellite instability (P = 0.024), and less glucose transporter 1 (P = 0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.


Subject(s)
Colorectal Neoplasms/genetics , MicroRNAs/biosynthesis , Neoplasms, Multiple Primary/genetics , RNA, Small Nucleolar/biosynthesis , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasms, Multiple Primary/pathology , Protein Array Analysis , Retrospective Studies
18.
Sci Rep ; 5: 10645, 2015 May 27.
Article in English | MEDLINE | ID: mdl-26013439

ABSTRACT

The incidence of colorectal cancer (CRC) in young patients (≤ 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linköping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/pathology , Adult , Age Factors , Aged , Biomarkers, Tumor/genetics , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/mortality , Databases, Factual , Demography , Disease-Free Survival , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Molecular Chaperones , Neoplasm Staging , Prognosis , Prolactin/genetics , Prolactin/metabolism , Proportional Hazards Models , Protein Interaction Maps , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Telomerase/genetics , Telomerase/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
20.
Medicine (Baltimore) ; 93(28): e266, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25526455

ABSTRACT

The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age≥70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/radiotherapy. Of the patients with colon cancer (n=467), 182 (39%) were aged <70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged ≥80 years. Of rectal cancer patients (n=554), 264 (48%) were aged <70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged ≥80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged ≥80 years had a higher 30-day mortality than younger patients (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.6-4.55; P=0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20-4.35, P=0.03) or rectal cancer (HR 1.72, 95% CI: 1.05-2.26, P=0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21-3.57, P=0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged ≥80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Colectomy/methods , Colorectal Neoplasms/therapy , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Incidence , Male , Neoplasm Recurrence, Local/epidemiology , Prognosis , Prospective Studies , Radiotherapy, Adjuvant , Survival Rate/trends , Sweden/epidemiology , Treatment Outcome
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