In vivo Recombinant Adenovirus-mediated p53 Gene Therapy in a Syngeneic Rat Model for Colorectal Cancer

The p53 gene has a significant role in controlling genomic stability of cancer. The purpose of this study was to evaluate the tumor response of allograft colorectal tumor treated with Ad5CMV-p53 in a syngeneic rat model. Two weeks after the inoculation of WB-2054-M5 tumor cells in the flank of rats, rats were randomly assigned by tumor size to one of three groups (n=18 in each): phosphate buffered saline (PBS), Ad5CMV, and Ad5CMV-p53. Recombinant adenovirus or PBS was administered through intratumoral injection at three divided doses every other day for 4 weeks. Apoptosis of the tumors was evaluated using TUNEL assay. After 2 and 4 weeks of treatment, the volume (cm3) of tumors in PBS, Ad5CMV, and Ad5CMV-p53 was as follows: 2 week: 1.66±0.43, 1.40±0.47, 0.75±0.26 (p<0.001), 4 week: 4.41±0.88, 3.93±1.86, 2.33±0.51 (p<0.001). Tumor growth showed no statistically significant difference between the PBS and Ad5CMV groups (6-week vol. p=0.32). The TUNEL assay results revealed more apparent apoptotic cells in Ad5CMV-p53-treated tumors than in other groups. Growth of allograft colorectal cancer in the syngeneic rat model was significantly suppressed by intratumoral Ad5CMV-p53 gene therapy. These results demonstrate that gene replacement therapy with p53 may provide a novel modality of treatment in conjunction with other present treatments for metastatic colorectal cancer

The role of primary tumor resection in colorectal cancer patients with asymptomatic, synchronous unresectable metastasis: Study protocol for a randomized controlled trial

BACKGROUND: Approximately 20 % of all patients with colorectal cancer are diagnosed as having Stage IV cancer; 80 % of these present with unresectable metastatic lesions. It is controversial whether chemotherapy with or without primary tumor resection (PTR) is effective for the treatment of patients with colorectal cancer with unresectable metastasis. Primary tumor resection could prevent tumor-related complications such as intestinal obstruction, perforation, bleeding, or fistula. Moreover, it may be associated with an increase in overall survival. However, surgery delays the use of systemic chemotherapy and affects the systemic spread of malignancy. METHODS/DESIGN: Patients with colon and upper rectal cancer patients with asymptomatic, synchronous, unresectable metastasis will be included after screening. They will be randomized and assigned to receive chemotherapy with or without PTR. The primary endpoint measure is 2-year overall survival rate and the secondary endpoint measures are primary tumor-related complications, quality of life, surgery-related morbidity and mortality, interventions with curative intent, chemotherapy-related toxicity, and total cost until death or study closing day. The authors hypothesize that the group receiving PTR following chemotherapy would show a 10 % improvement in 2-year overall survival, compared with the group receiving chemotherapy alone. The accrual period is 3 years and the follow-up period is 2 years. Based on the inequality design, a two-sided log-rank test with α-error of 0.05 and a power of 80 % was conducted. Allowing for a drop-out rate of 10 %, 480 patients (240 per group) will need to be recruited. Patients will be followed up at every 3 months for 3 years and then every 6 months for 2 years after the last patient has been randomized. DISCUSSION: This randomized controlled trial aims to investigate whether PTR with chemotherapy shows better overall survival than chemotherapy alone for patients with asymptomatic, synchronous unresectable metastasis. This trial is expected to provide evidence so support clear treatment guidelines for patients with colorectal cancer with asymptomatic, synchronous unresectable metastasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT01978249

Metastatic colon cancer of an ovarian cancer origin mimicking primary colon cancer: A case report

Metastatic colorectal cancer is rare and its origins are difficult to define if the gross features of colorectal cancer mimic primary colorectal cancer. However, accurate diagnosis is essential because the treatment and prognosis may vary depending on the origin of the cancer. This report is about a 74-year-old female patient with metastatic sigmoid colon cancer of ovarian origin that mimicked primary sigmoid colon cancer. She spent a 3-year period disease-free from ovarian cancer after surgery and adjuvant chemotherapy. At the time of initial diagnosis, the cancer was diagnosed as a primary sigmoid colon cancer, because the cancer appeared to be a solitary intra-luminal fungating mass. However, the final pathologic result showed that the cancer was metastatic sigmoid colon cancer of ovarian origin and it was confirmed by immunohistochemical staining of cytokeratins-7, -20, and Wilms tumor-1. Therefore, even if colorectal cancer is a single intra-luminal lesion, patients should be suspected of having metastatic colorectal cancer if they have other cancer histories. At this time, immunohistochemical staining using various cancer markers may be a useful tool to distinguish the origin of cancer

Thermal Frequency Reconfigurable Electromagnetic Absorber Using Phase Change Material

In this study, we propose a thermal frequency reconfigurable electromagnetic absorber using germanium telluride (GeTe) phase change material. Thermally-induced phase transition of GeTe from an amorphous high-resistive state to a crystalline low-resistive state by heating is used to change the resonant frequency of the absorber. For full-wave simulation, the electromagnetic properties of GeTe at 25 &deg;C and 250 &deg;C are characterized at 10 GHz under normal incidence for electromagnetic waves. The proposed absorber is designed based on the characterized electromagnetic parameters of GeTe. A circular unit cell is designed and GeTe is placed at a gap in the circle to maximize the switching range. The performance of the proposed electromagnetic absorber is numerically and experimentally demonstrated. Measurement results indicate that the absorption frequency changes from 10.23 GHz to 9.6 GHz when the GeTe film is altered from an amorphous state at room temperature to a crystalline state by heating the sample to 250 &deg;C. The absorptivity in these states is determined to be 91% and 92%, respectively

Docosahexaenoic acid inhibits insulin-induced activation of sterol regulatory-element binding protein 1 and cyclooxygenase-2 expression through upregulation of SIRT1 in human colon epithelial cells

Multiple lines of compelling evidence from clinical and population-based studies support that hyperinsulinemia often accompanying obesity-associated insulin insensitivity promotes colon carcinogenesis. Insulin can acetylate, thereby activating sterol regulator element-binding protein 1 (SREBP-1), a prime transcription factor responsible for expression of genes involved in lipogenesis. Moreover, SREBP-1 upregulates cyclooxygenase-2 (COX-2), a key player in inflammatory signaling. Docosahexaenoic acid (DHA), a representative omega-3 polyunsaturated fatty acid, has been known to negatively regulate SREBP-1, but the underlying molecular mechanism is not fully clarified yet. This prompted us to investigate whether DHA could inhibit insulin-induced activation of SREBP-1 and COX-2 expression in the context of its potential protective effect on obesity-induced inflammation and carcinogenesis. SIRT1, a NAD(+)-dependent histone/non-histone protein deacetylase, has been reported to inhibit intracellular signaling mediated by SREBP-1 through deacetylation of this transcription factor. We found that DHA induced SIRT1 expression in CCD841CoN human colon epithelial cells. DHA abrogated insulin-induced acetylation as well as expression of SREBP-1 and COX-2 upregulation. Insulin-induced stimulation of CCD841CoN cell migration was also inhbited by DHA. These effects mediated by DHA were attenuated by pharmacologic inhibition of SIRT1. Hyperinsulinemia or insulin resistance is considered to be associated with obesity-associated inflammation. Genetically obese (ob/ob)) mice showed higher colonic expression levels of both SREBP-1 and COX-2 than did normal lean mice. Likewise, expression of SREBP-1 and COX-2 was elevated in human colon tumor specimens compared with surrounding normal tissues. In conclusion, DHA may protect against obesity-associated inflammation and colon carcinogenesis by suppressing insulin-induced activation of SREBP-1 and expression of COX-2 through up-regulation of SIRT1. (C) 2014 Elsevier Inc. All rights reserved

Gastrointestinal autonomic nerve tumor in the lower rectum

Gastrointestinal autonomic nerve tumor (GANT) in the rectum is a subset of gastrointestinal stromal tumor (GIST). It’s a very rare mesenchymal tumor with neuronal differentiation of gastrointestinal tract. We experienced a 34-year-old female patient with GANT in the lower rectum. She was referred to our hospital owing to rectal bleeding, but didn’t have other symptoms such as abdominal pain and constipation. On digital rectal examination, a round and smooth submucosal tumor at posterior wall of the rectum was palpated approximately 5 cm above the anal verge. The mass measured approximately 5 cm in diameter and was not fixed to the underlying structures. Colonoscopy, abdomino-pelvic computed tomography scan, and core needle biopsy were performed. Given the impression of GIST, it was assumed that the patient underwent low anterior resection with double stapling technique. The tumor, a yellow-grayish colored mass, was homogenous and didn’t have hemorrhagic necrosis. Diagnosis of GANT was based on histological, immunohistochemical staining, and electron microscopy. The patient did not receive any adjuvant therapy and was discharged without complications on the tenth postoperative day

Measurement of human peritoneal surface area using artificial intelligence software in abdominal computed tomography

Purpose The calculation of the intraperitoneal organ surface area is important for understanding their anatomical structure and for conducting basic and clinical studies on diseases related to the peritoneum. To measure the intraperitoneal surface area in a living body by applying artificial intelligence (AI) techniques to the abdominal cavity using computed tomography and to prepare clinical indicators for application to the abdominal cavity. Methods Computed tomography images of ten adult males and females with a healthy body mass index and ten adults diagnosed with colon cancer were analyzed to determine the peritoneal and intraperitoneal surface areas of the organs. The peritoneal surface was segmented and three-dimensionally modeled using AI medical imaging software. In addition to manual work, three-dimensional editing, filtering, and connectivity checks were performed to improve work efficiency and accuracy. The colon and small intestine surface areas were calculated using the mean length and diameter. The abdominal cavity surface area was defined as the sum of the intraperitoneal area and the surface areas of each organ. Results The mean peritoneal surface area of all participants was measured as 10,039±241 cm2 (males 10,224±171 cm2 and females 9,854±134 cm2). Males had a 3.7% larger peritoneal surface area than females, with a statistically significant difference (P<0.001). Conclusion The abdominal cavity surface area can be measured using AI techniques and is expected to be used as basic data for clinical applications

Effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer: a cohort study

Abstract Background Mistletoe extract, used as a complementary chemotherapeutic agent for cancer patients, has anticancer effects against various malignancies. The aim of the present study was to evaluate the effect of mistletoe extract (Abnoba Viscum Q®) on tumor responses to neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer. Methods This study included patients with rectal cancer who underwent NCRT between January 2018 and July 2020. In the mistletoe group (MG), the patients were administered Abnoba Viscum Q® subcutaneously during chemoradiotherapy—maintained just before surgery. Patient demographics, clinical outcomes, histopathological outcomes, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay results were compared between the MG and non-mistletoe group (NMG). Two rectal cancer cell lines (SNU-503 and SNU-503R80Gy) were treated with Abnoba Viscum Q® to assess its mechanistic effects in vivo. Results Overall, the study included 52 patients (MG: n = 15; NMG: n = 37). Baseline demographics between the two groups were similar, except carbohydrate antigen 19-9 levels and tumor location from the anal verge. There was no difference in the clinical stage between the two groups. A better tumor response in the MG, relative to the NMG, was observed with respect to tumor regression grade (TRG), T stage, and overall tumor–node–metastasis stage. Tumor response was significantly better in the MG than in the NMG in terms of pathologic complete response rate (53.3% vs. 21.6%, P = 0.044), good TRG response (66.7% vs. 32.4%, P = 0.024), T downstaging (86.7% vs. 43.2%, P = 0.004), and overall downstaging (86.7% vs. 56.8%, P = 0.040). The toxicities during NCRT were minimal in both groups. More apoptotic cells were noted in MG samples than in the NMG samples on TUNEL staining. Cleaved caspase-3 level following treatment with Abnoba Viscum Q® was higher in SNU-503R80Gy cells than in SNU-503 cells. Conclusion Patients treated with chemoradiation combined with mistletoe extract showed better outcomes than patients not treated with mistletoe extract in terms of tumor responses. This diversity in treatment may improve the efficacy of NCRT, leading to better oncologic outcomes. Prospective and randomized studies with long-term follow-up are warranted to confirm and extend these results

An analysis of the outcomes of totally implantable access port implantation performed by surgical residents

Purpose This study aimed to investigate the clinical outcomes after totally implantable access port (TIAP) implantation performed by general surgery residents in patients with colorectal cancer. Methods A total of 291 consecutive patients who underwent TIAP implantations were evaluated. The patients were divided into three groups: second-, third-, and fourth-grade residents. Results The mean follow-up was 22.1 months (range, 1–87 months). The total times of operation, puncture, and cannulation decreased as the resident grade increased (P<0.001). Early complications significantly decreased with higher resident grades (P=0.039). The non-use of ultrasonography and non-use of C-arm were identified as independent risk factors for complications. Resident grades between second and third (P=0.005) and between second and fourth (P=0.041) were identified as independent risk factors for optimal tip position. Conclusion TIAP implantation can be safely and effectively performed by residents. Low-grade residents were associated with early complications

Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis

Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD(+)-dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Moreover, leptin induced up-regulation of SIRT1 in human colon cancer (HCT-116) cells. Leptin stimulated migration and invasion of cultured HCT-116 cells and tumor growth in the xenograft assay, and these effects were abrogated by a SIRT1 inhibitor sirtinol, suggesting that SIRT1 plays a role in leptin-induced colon carcinogenesis. Leptin-induced SIRT1 expression was regulated by the redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2). Leptin stimulated nuclear accumulation of Nrf2 as well as its binding to the antioxidant response elements located in the SIRT1 promoter. Moreover, siRNA knockdown of Nrf2 abrogated the leptin-induced SIRT1 expression. Notably, SIRT1 was significantly reduced in colon tissues of Nrf2-null mice, lending further support to Nrf2-dependent SIRT1 expression. Expression of leptin, Nrf2 and SIRT1 was coordinately increased in human colon tumor tissues. In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression