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1.
Nat Commun ; 15(1): 10, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38169465

ABSTRACT

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.


Subject(s)
Skin, Artificial , Humans , Bionics , Touch/physiology , Skin , Wound Healing , Sense Organs
2.
BMC Gastroenterol ; 23(1): 39, 2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36782150

ABSTRACT

BACKGROUND: An underweight individual is defined as one whose Body Mass Index (BMI) is < 18.5 kg/m2. Currently, the prognosis in patients with colorectal cancer (CRC) who are also underweight is unclear. METHODS: Information on South Korean patients who underwent curative resection for CRC without distant metastasis was collected from health insurance registry data between January 2014 and December 2016. We compared the overall survival (OS) of underweight and non-underweight (BMI ≥ 18.5 kg/m2) patients after adjusting for confounders using propensity score matching. A nomogram to predict OS in the underweight group was constructed using the significant risk factors identified in multivariate analysis. The predictive and discriminative capabilities of the nomogram for predicting 3- and 5-year OS in the underweight group were validated and compared with those of the tumor, node, and metastasis (TNM) staging system in the training and validation sets. RESULTS: A total of 23,803 (93.6%) and 1,644 (6.4%) patients were assigned to the non-underweight and underweight groups, respectively. OS was significantly worse in the underweight group than in the non-underweight group for each pathological stage (non-underweight vs. underweight: stage I, 90.1% vs. 77.1%; stage IIA, 85.3% vs. 67.3%; stage IIB/C, 74.9% vs. 52.1%; and stage III, 73.2% vs. 59.4%, P < 0.001). The calibration plots demonstrated that the nomogram exhibited satisfactory consistency with the actual results. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) of the nomogram exhibited better discriminatory capability than those of the TNM staging system (C-index, nomogram versus TNM staging system: training set, 0.713 versus 0.564, P < 0.001; validation set, 0.691 versus 0.548, P < 0.001; AUC for 3- and 5- year OS, nomogram versus TNM staging system: training set, 0.748 and 0.741 versus 0.610 and 0.601; validation set, 0.715 and 0.753 versus 0.586 and 0.579, respectively). CONCLUSIONS: Underweight patients had worse OS than non-underweight patients for all stages of CRC. Our nomogram can guide prognostic predictions and the treatment plan for underweight patients with CRC.


Subject(s)
Colorectal Neoplasms , Nomograms , Humans , Neoplasm Staging , Prognosis , Risk Factors , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology
3.
Int J Colorectal Dis ; 38(1): 42, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36790520

ABSTRACT

PURPOSE: To investigate oncologic outcomes including overall survival and disease-free survival depending on the extent of lymphadenectomy (D3 versus D2) by comparing D3 and D2 lymphadenectomy in patients with clinical stage 2/3 right colon cancer. METHODS: Consecutive series of patients who underwent radical resection for right colon cancer at our three hospitals between January 2015 and June 2018 were retrospectively analyzed. Study cohorts were divided into two groups: D3 group and D2 group. Oncologic, pathologic, and perioperative outcomes of the two groups were compared. RESULTS: A total of 295 patients (167 in the D2 group and 128 in the D3 group) were included in this study. Patients' characteristics showed no significant difference between the two groups. The median number of harvested lymph nodes was significantly higher in the D3 group than in the D2 group. The rate of complications was not significantly different between the two groups except for chyle leakage, which was more frequent in the D3 group. Five-year disease-free survival was 90.2% (95% CI: 84.8-95.9%) in the D3 group, which was significantly (p = 0.028) higher than that (80.5%, 95% CI: 74-87.5%) in the D2 group. There was no significant difference in overall survival between the two groups. CONCLUSION: Our results indicate that D3 lymphadenectomy is associated with more favorable 5-year disease-free survival than D2 lymphadenectomy for patients with stage 2/3 right-sided colon cancer. D3 lymphadenectomy might improve oncologic outcomes in consideration of the recurrence rate.


Subject(s)
Colonic Neoplasms , Laparoscopy , Humans , Retrospective Studies , Laparoscopy/methods , Lymph Node Excision/methods , Colonic Neoplasms/pathology , Lymph Nodes/surgery , Lymph Nodes/pathology , Colectomy/adverse effects , Colectomy/methods
4.
Ann Surg Treat Res ; 102(4): 234-240, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35475228

ABSTRACT

Purpose: There are few reports on outcomes following surgical repair of recurrent rectal prolapse. The purpose of this study was to examine surgical outcomes for recurrent rectal prolapse. Methods: We conducted a multicenter retrospective study of patients who underwent surgery for recurrent rectal prolapse. This study used data collected by the Korean Anorectal Physiology and Pelvic Floor Disorder Study Group. Results: A total of 166 patients who underwent surgery for recurrent rectal prolapse were registered retrospectively between 2011 and 2016 in 8 referral hospitals. Among them, 153 patients were finally enrolled, excluding 13 patients who were not followed up postoperatively. Median follow-up duration was 40 months (range, 0.2-129.3 months). Methods of surgical repair for recurrent rectal prolapse included perineal approach (n = 96) and abdominal approach (n = 57). Postoperative complications occurred in 16 patients (10.5%). There was no significant difference in complication rate between perineal and abdominal approach groups. While patients who underwent the perineal approach were older and more fragile, patients who underwent the abdominal approach had longer operation time and admission days (P < 0.05). Overall, 29 patients (19.0%) showed re-recurrence after surgery. Among variables, none affected the re-recurrence. Conclusion: For the recurrent rectal prolapse, the perineal approach is used for the old and fragile patients. The postoperative complications and re-recurrence rate between perineal and abdominal approach were not different significantly. No factor including surgical method affected re-recurrence for recurrent rectal prolapse.

5.
Cancers (Basel) ; 14(5)2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35267605

ABSTRACT

In colorectal cancer, whereas mucinous adenocarcinoma (MAC) has several poor clinical prognostic factors compared to adenocarcinoma (AC), the prognosis of MAC remains controversial. We evaluated the prognosis of MAC without distant metastasis and the effects of adjuvant chemotherapy using health insurance registry data managed by South Korea. Patients with colorectal cancer between January 2014 and December 2016 were included (AC, 22,050 [96.8%]; MAC, 729 [3.2%]). We observed no difference in overall survival (OS) between AC and MAC in stages I and II. However, MAC showed a worse OS than AC in stage III disease, especially in patients administered chemotherapy (p < 0.001). These findings persisted after propensity score matching of clinical characteristics between AC and MAC. In addition, transcriptome analysis of The Cancer Genome Atlas (TCGA) data showed increased chemoresistance-associated pathways in MAC compared to AC. In consensus molecular subtypes (CMS) classification, unlike in AC, CMSs 1, 3, and 4 comprised most of MAC and the proportions of CMSs 3 and 4 increased with stage progression. These results suggest clues to overcome resistance to chemotherapy and develop targeted treatments in MAC.

6.
Asia Pac J Clin Oncol ; 18(4): 378-387, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34310853

ABSTRACT

BACKGROUND: The involvement of resection margins after rectal cancer surgery by malignant tumors is a negative prognostic factor. Therefore, it is important to analyze treatment outcomes and establish adjuvant therapy. METHODS: The Health Insurance Review and Assessment Service collects data from medical institutions in South Korea. We reviewed the database of this prospectively collected cohort for patients who underwent curative resection for rectal cancer. RESULTS: Of the 5,620 patients, 113 (2.0%) were diagnosed with resection margin involvement after surgery. The resection margins of patients with mid-rectal cancer, pathologic stage III, mucinous/signet ring cell carcinoma, and undergoing emergency surgery were more frequently involved. Neoadjuvant chemoradiotherapy was a significant preventive factor for resection margin involvement (odds ratio = 0.53; 95% confidence interval [CI], 0.32-0.87; p = 0.012). The OS of patients with adjuvant treatment was better than that of patients without adjuvant treatment (5-year overall survival [OS]: 62.8% vs. 46.3%, p = 0.02). The administration of chemoradiotherapy was also significantly associated with better OS (hazard ratio = 0.36; 95% CI, 0.17-0.77; p = 0.009). CONCLUSION: Efforts to acquire wider resection margins are necessary for patients with mid-rectal cancer, pathologic stage III, mucinous/signet ring cell carcinoma, and emergency surgery. Neoadjuvant chemoradiotherapy was a significant preventive factor for involved resection margin. Patients with resection margin involvement showed better OS after adjuvant treatment than those without adjuvant treatment. The adjuvant chemoradiotherapy was helpful to prevent the worse prognosis of these patients.


Subject(s)
Carcinoma, Signet Ring Cell , Rectal Neoplasms , Chemoradiotherapy, Adjuvant , Cohort Studies , Humans , Margins of Excision , Neoadjuvant Therapy , Neoplasm Staging , Rectal Neoplasms/pathology , Retrospective Studies , Treatment Outcome
7.
Ann Surg Treat Res ; 100(5): 282-290, 2021 May.
Article in English | MEDLINE | ID: mdl-34012946

ABSTRACT

PURPOSE: Neoadjuvant chemoradiotherapy has been accepted as a standard treatment for stage II-III rectal cancer. This study aimed to evaluate the clinical characteristics of patients who underwent neoadjuvant chemoradiotherapy for rectal cancer and effects on overall survival (OS) of neoadjuvant chemoradiotherapy in South Korea. METHODS: Patients who underwent curative resection for rectal cancer from 2014 to 2016 were retrospectively reviewed from the database of the National Quality Assessment program in South Korea. Patients were categorized into the upfront surgery group and neoadjuvant chemoradiotherapy group. We evaluated factors associated with the administration of neoadjuvant chemoradiotherapy and its effects on OS. Inverse probability of treatment weighting was performed to account for baseline differences between subgroups. RESULTS: A total of 6,141 patients were categorized into the upfront surgery group (n = 4,237) and neoadjuvant chemoradiotherapy group (n = 1,904). The neoadjuvant chemoradiotherapy was more frequently administered to male, midrectal cancer, and younger patients. In the neoadjuvant chemoradiotherapy group, old age, underweight, and pathologic stage were significant risk factors of OS, and male sex, the level of tumor and clinical stages were not associated with OS. After adjustment, the OS of the neoadjuvant chemoradiotherapy group followed the OS of the upfront surgery group of the same pathologic stage. CONCLUSION: Male sex and the level of tumor were not related to the OS of rectal cancer patients with neoadjuvant chemoradiotherapy. The OS of patients who underwent neoadjuvant chemoradiotherapy was decided by their pathologic stages regardless of clinical stages.

8.
Asian J Surg ; 44(10): 1278-1282, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33752988

ABSTRACT

BACKGROUND: D3 lymph node dissection is becoming the standard procedure for the treatment of advanced right colon cancer and has shown increasing evidence of its oncologic benefit. However, a clear indication for its application is lacking and data on this topic is unsatisfactory. Thus, the necessity for D3 lymph node dissection in clinical stage I right colon cancer remains controversial. METHODS: We retrospectively analyzed data from clinical stage I right colon cancer patients who underwent radical surgery at three hospitals of Korea university medical center between January 2015 and June 2018. We compared surgical complications and short-term oncologic outcomes between D2 and D3 lymph node dissections in these patients. RESULTS: Among 512 patients, 122 (23.8%) were clinical stage I. Of these, 88 and 34 patients received D2 and D3 lymph node dissection, respectively. There were no statistically significant differences in clinicopathologic variables and surgical outcomes between the two groups. Upstaging occurred in 16 patients (47.1%) in the D3 group and 23 patients (26.1%) in the D2 group. There were four recurrences in the D2 group but no recurrence in the D3 group. Log-rank tests showed no statistically significant difference in disease-free survival rates between the two groups (p = 0.210). CONCLUSION: There was no significant difference in disease-free survival rates between D2 and D3 lymph node dissection in clinical stage I right colon cancer patients. However, recurrence occurred in the D2 group. Efforts to improve the accuracy of clinical staging are required and more studies with better quality are needed.


Subject(s)
Colonic Neoplasms , Laparoscopy , Colonic Neoplasms/surgery , Humans , Lymph Node Excision , Neoplasm Recurrence, Local/epidemiology , Retrospective Studies
9.
ANZ J Surg ; 91(4): E183-E189, 2021 04.
Article in English | MEDLINE | ID: mdl-33634960

ABSTRACT

BACKGROUND: Resectability of liver metastasis is important to establish a treatment strategy for patients with colorectal cancer. We aimed to evaluate the effect of the distance from metastasis to the centre of the liver on surgical outcomes and survival after hepatectomy. METHODS: The clinical data of a total of 155 patients who underwent hepatectomy for colorectal cancer with liver metastasis were retrospectively reviewed. We measured the minimal length from metastasis to the bifurcation of the portal vein at the primary branch of the Glissonean tree and defined it as 'centrality'. The postoperative outcomes and survival among the patients were then analysed. RESULTS: Anatomic resections were more frequently performed, and the operative time was longer in the patients with high centrality (≤1.5 cm) than in the patients with low centrality (>1.5 cm). A size of ≥5 cm for the largest lesion, a number of lesions of ≥3 and centrality of ≤1.5 cm were found to be the independent risk factors of a positive resection margin after hepatectomy. The patients with high centrality showed worse recurrence-free survival than those with low centrality; however, there was no significant difference found in the overall survival. In the multivariate analysis, high centrality was not found to be associated with worse recurrence-free and overall survival. CONCLUSION: Centrality significantly affected the surgical outcomes and treatment strategy for liver metastasis but did not influence the survival of the patients with colorectal cancer. Active efforts through surgical resections are important to treat liver metastasis of high centrality.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Colorectal Neoplasms/surgery , Hepatectomy , Humans , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Survival Rate , Treatment Outcome
10.
Nano Lett ; 21(2): 1132-1140, 2021 Jan 27.
Article in English | MEDLINE | ID: mdl-33439663

ABSTRACT

Ideal electromagnetic (EM) wave absorbers can absorb all incident EM waves, regardless of the incident direction, polarization, and frequency. Absorptance and reflectance are intrinsic material properties strongly correlated with electrical conductivity; hence, achieving perfect absorptance with zero reflectance is challenging. Herein, we present a design strategy for preparing a nearly ideal EM absorber based on a layered metal that maximizes absorption by utilizing multiple internal reflections and minimizes reflection using a monotonic gradient of intrinsic impedance. This approach was experimentally verified using aluminum nanoflakes prepared via topochemical etching of lithium from Li9Al4, and the impedance-graded structure was obtained through the size-based sorting behavior of aluminum nanoflakes sinking in dispersion. Unlike in traditional shielding materials, strong absorption (26.76 dB) and negligible reflectivity (0.04 dB) with a ratio of >103 can be achieved in a 120 µm thick film. Overall, our findings exhibit potential for developing a novel class of antireflective shielding materials.

11.
Ann Surg Treat Res ; 100(1): 25-32, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33457394

ABSTRACT

PURPOSE: The prognosis of young colorectal cancer (CRC) patients has not fully been addressed. The prognostic significance of systemic inflammatory markers was examined in those patients. METHODS: A total of 965 patients with resectable CRC were divided into young (≤ 50 years, n = 101) and old groups (> 51 years, n = 864). Neutrophil-to-lymphocyte ratio (NLR) > 5, derived NLR (dNLR) > 3, lymphocyte-to-monocyte ratio (LMR) < 2, platelet-to-lymphocyte ratio (PLR) > 150, and prognostic nutritional index (PNI) < 45 were analyzed for prognosis. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test. A multivariate analysis was performed using a Cox proportional hazards regression model. RESULTS: In the young group, NLR > 5, LMR < 2, and PNI < 45 were significantly associated with OS with univariate analyses. dNLR > 3 and those markers showed significance for PFS. LMR < 2 was a significant marker for poor PFS (hazard ratio [HR], 5.81; P = 0.020) in the multivariate analysis. In the old group, all inflammatory markers were significantly associated with OS and PFS with univariate analyses. LMR < 2 (HR, 2.66; P = 0.016) and PNI < 45 (HR, 2.14; P = 0.016) were independently associated with OS in multivariate analyses. PLR > 150 (HR, 1.45; P = 0.036) and PNI < 45 (HR, 1.73; P = 0.002) were significant markers for PFS. CONCLUSION: Systemic inflammation might be one of biologic factors that influence on prognosis of young CRC.

12.
Ann Coloproctol ; 37(2): 75-84, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32674551

ABSTRACT

Infectious complications are the biggest problem during bowel surgery, and one of the approaches to minimize them is the bowel cleaning method. It was expected that bowel cleaning could facilitate bowel manipulation as well as prevent infectious complications and further reduce anastomotic leakage. In the past, with the development of antibiotics, bowel cleaning and oral antibiotics (OA) were used together. However, with the success of emergency surgery and Enhanced Recovery After Surgery, bowel cleaning was not routinely performed. Consequently, bowel cleaning using OA was gradually no longer used. Recently, there have been reports that only bowel cleaning is not helpful in reducing infectious complications such as surgical site infection (SSI) compared to OA and bowel cleaning. Accordingly, in order to reduce SSI, guidelines are changing the trend of only intestinal cleaning. However, a consistent regimen has not yet been established, and there is still controversy depending on the location of the lesion and the surgical method. Moreover, complications such as Clostridium difficile infection have not been clearly analyzed. In the present review, we considered the overall bowel preparation trends and identified the areas that require further research.

13.
Nat Commun ; 11(1): 1574, 2020 Mar 27.
Article in English | MEDLINE | ID: mdl-32221285

ABSTRACT

Ultra-thin two-dimensional semiconducting crystals in their monolayer and few-layer forms show promising aspects in nanoelectronic applications. However, the ultra-thin nature of two-dimensional crystals inevitably results in high contact resistance from limited channel/contact volume as well as device-to-device variability, which seriously limit reliable applications using two-dimensional semiconductors. Here, we incorporate rather thick two-dimensional layered semiconducting crystals for reliable vertical diodes showing excellent Ohmic and Schottky contacts. Using the vertical transport of WSe2, we demonstrate devices which are functional at various frequency ranges from megahertz AM demodulation of audio signals, to gigahertz rectification for fifth-generation wireless electronics, to ultraviolet-visible photodetection. The WSe2 exhibits an excellent Ohmic contact to bottom platinum electrode with record-low contact resistance (~50 Ω) and an exemplary Schottky junction to top transparent conducting oxide electrode. Our semitransparent vertical WSe2 Schottky diodes could be a key component of future high frequency electronics in the era of fifth-generation wireless communication.

14.
Asian J Surg ; 43(2): 438-446, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31439461

ABSTRACT

BACKGROUND: The aim of this study was to identify predictive factors for the recurrence of colorectal cancer liver metastasis (CRLM) and then to develop a corresponding novel scoring system that should improve the sensitivity of predicting recurrence in patients with CRLM. METHODS: A total of 295 consecutive CRLM patients were enrolled in our institution between January 2002 and December 2015. Multivariate analyses were performed to identify the variables associated with disease recurrence and established the novel scoring system based on it. RESULTS: The scoring system considered seven variables: synchronosity, CA19-9 level, number of liver metastasis, largest size of liver metastasis, resection margin of hepatic lesion, neutrophil-to-lymphocyte ratio and prognostic nutritional index. The area under the curve of ROC was 0.824 (95% confidence interval 0.767-0.882); the sensitivity of our scoring system was 87.9%, specificity was 66.7%, positive predictive value was 20.6%, and negative predictive value was 20.9%. CONCLUSION: For patients with CRLM undergoing curative hepatic resection, our novel scoring system would improve the sensitivity for prediction of disease recurrence in Case of CRLM patients.


Subject(s)
Colorectal Neoplasms/pathology , Diagnostic Techniques, Digestive System , Liver Neoplasms/secondary , Neoplasm Recurrence, Local , Adult , Aged , Aged, 80 and over , CA-19-9 Antigen , Disease Progression , Female , Hepatectomy , Humans , Leukocyte Count , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Lymphocytes , Male , Margins of Excision , Middle Aged , Neutrophils , Nutrition Assessment , Predictive Value of Tests , ROC Curve , Sensitivity and Specificity
15.
PLoS One ; 14(5): e0216474, 2019.
Article in English | MEDLINE | ID: mdl-31120917

ABSTRACT

A 26-GHz transmitter front-end is designed using 65 nm CMOS technology. The double frequency conversion transmitter consists of an intermediate frequency(IF) mixer, an millimeter-wave(mm-wave) mixer, and a pre-power amplifier. A double quadrature architecture is employed to accomplish image rejection without using an image rejection filter for the first time in the mm-wave frequency band. The IF mixer cores are designed as harmonic rejection mixers to avoid using IF filters. The measured conversion gain is 26.85±0.65 dB, with LO2 (IF LO) at 1-1.5 GHz and 26.9±0.6 dB with LO1 (mm-wave LO) at 27-29 GHz. The measured output return loss is less than -10 dB at 25.7-27.2 GHz. The output 1-dB compression point and the saturation output power measured at 26 GHz are 10 dBm and 14.1 dBm, respectively. The output-referred third-order intercept point (OIP3) measured at 26 GHz is 15.76 dBm. The third-order distortion, suppressed by the harmonic rejection mixer, is -60.5 dBc at an output power of 10 dBm. The error vector magnitude measured for OFDM 16-QAM with a 110-MHz signal bandwidth is -17.7 dB at an average output power of 3.5 dBm. The total power consumption of the proposed 26-GHz transmitter front-end is 267 mW, and it occupies a chip area of 2.31 mm2.


Subject(s)
Amplifiers, Electronic , Radio Waves , Wireless Technology
16.
Nat Commun ; 10(1): 653, 2019 02 08.
Article in English | MEDLINE | ID: mdl-30737393

ABSTRACT

The ideal combination of high optical transparency and high electrical conductivity, especially at very low frequencies of less than the gigahertz (GHz) order, such as the radiofrequencies at which electronic devices operate (tens of kHz to hundreds of GHz), is fundamental incompatibility, which creates a barrier to the realization of enhanced user interfaces and 'device-to-device integration.' Herein, we present a design strategy for preparing a megahertz (MHz)-transparent conductor, based on a plasma frequency controlled by the electrical conductivity, with the ultimate goal of device-to-device integration through electromagnetic wave transmittance. This approach is verified experimentally using a conducting polymer, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), the microstructure of which is manipulated by employing a solution process. The use of a transparent conducting polymer as an electrode enables the fabrication of a fully functional touch-controlled display device and magnetic resonance imaging (MRI)-compatible biomedical monitoring device, which would open up a new paradigm for transparent conductors.

17.
PLoS One ; 13(10): e0205449, 2018.
Article in English | MEDLINE | ID: mdl-30308035

ABSTRACT

Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin-treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.


Subject(s)
Colorectal Neoplasms/genetics , Interleukin-6/genetics , Interleukin-6/metabolism , Metformin/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , Humans , Neoplasm Metastasis
18.
Medicine (Baltimore) ; 97(9): e0019, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29489646

ABSTRACT

The colorectal cancer (CRC) patients with microsatellite instability (MSI) have distinct clinicopathological characteristics consisting of factors predicting positive and negative outcomes, such as a high lymph node harvest and poor differentiation. In this study, we measured the value of MSI as a prognostic factor after controlling for these discrepant factors. A total of 603 patients who underwent curative surgery for stages I to III colorectal cancer were enrolled. The patients were divided into microsatellite instability high (MSI-H) and microsatellite stable/microsatellite instability low (MSS/MSI-L) groups. Propensity score matching was used to match clinicopathological factors between the 2 groups. MSI-H patients had a high lymph node harvest (median: 31.0 vs 23.0, P < .001), earlier-stage tumors (P < .001), advanced T stage (89.3% vs 74.0%, P = .018), and poor differentiation (19.6% vs 2.0%, P < .001). Survival analysis showed better survival in the MSI-H group, but the difference was not statistically significant (P = .126). Propensity score matching was performed for significant prognostic factors identified by Cox hazard regression. After the matching, the survival difference by MSI status was estimated to be larger than before, and reached statistical significance (P = .045). In conclusion, after controlling for pathological characteristics, MSI-H could be a potent prognostic factor regarding patient survival.


Subject(s)
Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Microsatellite Instability , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Propensity Score , Proportional Hazards Models , Survival Analysis
19.
Ann Surg Treat Res ; 94(1): 36-43, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29333424

ABSTRACT

PURPOSE: Because data as a basis for the determination of proper age and modality for screening of colorectal neoplasms is lacking, we evaluated detection rates and anatomical distribution of colorectal neoplasms according to age in healthy individuals who underwent total colonoscopy for health checkup. METHODS: A total of 16,100 cases that had received the colonoscopic examination from January to December in 2014 were analyzed. The total number of individuals who received total colonoscopy were divided by the number of individuals harboring colorectal adenoma to calculate the detection rate of colorectal adenoma. Individuals ≤50 years old were classified as young-age group and aged >50 were old-age group. Differences in anatomical locations of colorectal neoplasms were analyzed in the 2 age groups by chi-square test. Risk factors for colorectal adenoma in each age group were analyzed using univariate and multivariate logistic regression analyses. RESULTS: Detection rates of colorectal adenoma were 13.7% in all cases and 12.8% for those in their 40's. The main anatomical location of colorectal adenoma was proximal colon in both age groups (P < 0.001). Hyperplastic polyp was mainly distributed to the distal colon in both age groups (P < 0.001). Distal colon was the major site for colorectal cancer in the old-age group (P = 0.001). Proximal location of neoplasms was a risk factor for colorectal adenoma in both age groups with multivariate analysis. CONCLUSION: These data could be the bases for earlier initiation of screening for colorectal neoplasms with total colonoscopy to detect clinically significant colorectal polyps.

20.
Anticancer Res ; 38(2): 787-794, 2018 02.
Article in English | MEDLINE | ID: mdl-29374703

ABSTRACT

BACKGROUND/AIM: The aim of this study was to investigate the role of transglutaminase 2 (TGM2) in colorectal cancer stem cells (CCSCs). MATERIALS AND METHODS: We used the TU12 cell line possessing CD133-expressing CCSCs. After isolating CD133 (-) and CD133 (+) CCSCs, we overexpressed and knocked-down TGM2 to investigate its role in human CCSCs. RESULTS: The expression level of TGM2 was 25-fold higher in tumorigenic cells than non-tumorigenic cells. We found that knockdown of TGM2 by specific RNA interference markedly inhibited cell growth and caused down-regulation of the stemness markers, CD133, SOX2, and ß-catenin. We further demonstrated that knockdown of TGM2 inhibited cell metastatic abilities by down-regulating N-cadherin and vimentin and up-regulating E-cadherin. These findings revealed that TGM2 expression is markedly increased in human colorectal cancer and that down-regulation of TGM2 in tumors may serve as a treatment for colorectal cancer patients. Therefore, this study indicate that TGM2 affects the metastatic potential and stemness of CCSCs by regulating EMT- and stemness-related proteins. CONCLUSION: The metastatic potential of CSCs arises from highly expressed TGM2.


Subject(s)
Colorectal Neoplasms/enzymology , GTP-Binding Proteins/biosynthesis , Neoplastic Stem Cells/enzymology , Transglutaminases/biosynthesis , AC133 Antigen/biosynthesis , Antigens, CD/metabolism , Biomarkers, Tumor , Cadherins/metabolism , Cell Line, Tumor , Cell Movement/physiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Down-Regulation , Epithelial-Mesenchymal Transition , GTP-Binding Proteins/genetics , GTP-Binding Proteins/metabolism , Gene Knockdown Techniques , Humans , Immunohistochemistry , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplastic Stem Cells/pathology , Protein Glutamine gamma Glutamyltransferase 2 , Transglutaminases/genetics , Transglutaminases/metabolism , Tumor Cells, Cultured , Vimentin/metabolism
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