The structural integrity of valves that are used to control cooling waters in the primary coolant loop that prevents boiling within the reactor in a nuclear power plant must be capable of withstanding earthquakes or other dangerous situations. In this study, numerical analyses using a finite element method, that is, static and dynamic analyses according to the rigid or flexible characteristics of the dynamic properties of a 200A butterfly valve, were performed according to the KEPIC MFA. An experimental vibration test was also carried out in order to verify the results from the modal analysis, in which a validated finite element model was obtained via a model-updating method that considers changes in the in situ experimental data. By using a validated finite element model, the equivalent static load under SSE conditions stipulated by the KEPIC MFA gave a stress of 135 MPa that occurred at the connections of the stem and body. A larger stress of 183 MPa was induced when we used a CQC method with a design response spectrum that uses 2% damping ratio. These values were lower than the allowable strength of the materials used for manufacturing the butterfly valve, and, therefore, its structural safety met the KEPIC MFA requirements.
The intracorporeal reconstruction after laparoscopic gastrectomy can minimize postoperative pain, and give better cosmetic effect, while it may have technical difficulties and require the learning curve. This study aimed to analyze the surgical outcome of intracorporeal reconstruction according to the surgeon's experience comparing with extracorporeal procedure.
Materials and Methods
From January 2009 to September 2011, intracorporeal reconstruction in laparoscopic surgery for gastric cancer was performed for 71 patients (Intra group). During same period, 231 patients underwent laparoscopy-assisted gastrectomy (Extra group). These patients were classified into initial (1st to 20th case of intra group), intermediate (21th to 46th case), and experienced (after 47th case) phases.
Intracorporeal procedures included 35 cases of Billroth-I, 30 Billroth-II and 6 Roux en Y reconstructions. In the initial phase, operation time (P=0.022) were significantly longer for the patients of intra group than them of extra group. Although the difference was not significant, the length of hospital stay was longer and complication rate was higher in the intra group. In intermediate and experienced phases, there was no difference between two groups in operation time and hospital stay. In these phases, complication rate was lower in the intra group than the extra group (3.9% versus 9.7%). The pain scale was significantly lower post operation day 5 in the intra group.
Intracorporeal reconstruction after laparoscopic distal gastrectomy was feasible and safe, and the technique was stabilized after 20th case if the surgeon has sufficient experiences when we compared it with extracorporeal reconstruction.
Intracorporeal; Extracorporeal; Billorth I; Billroth II; Roux en Y
In contrast to mitochondria in healthy cells, which utilize oxidative phosphorylation, malignant cells undergo elevated glycolysis for energy production using glucose. The objectives of this study were to evaluate whether the expression of various molecules, including pyruvate dehydrogenase kinase-1 (PDK-1), is involved in the altered glucose metabolism associated with gastric cancer prognosis and to assess the role of a therapeutic agent in targeting glucose metabolism in gastric cancer. Immunohistochemistry was performed on gastric cancer tissues obtained from 152 patients who underwent curative resection to assess the expression of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an in vitro analysis, the lactate production and glucose uptake levels, cellular viability and 5-fluorouracil (5-FU) responses were evaluated before and after treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and PDK-1 expression was significantly associated with tumor progression, although only PDK-1 expression was an independent prognostic factor for patients who received 5-FU adjuvant treatment. There was no significant difference in cell viability between the HEK293 and gastric cancer cell lines following DCA treatment. However, DCA treatment reduced lactate production and increased responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK-1-expressing gastric cancers.
gastric neoplasm; chemotherapy; pyruvate dehydrogenase; prognosis
The goal of this study was to assess the correlation between the Helicobacter pylori status of patients who underwent curative resection for gastric adenocarcinoma and their prognosis in Eastern societies where H. pylori infection is prevalent.
Between 2006 and 2007, 192 patients who had a curative resection for the treatment of gastric adenocarcinoma were enrolled in the study. Of these patients, 18 were excluded due to an inexact evaluation of the H. pylori status, thereby leaving 174 patients in the final analysis. Serologic testing for H. pylori was assessed using an enzyme-linked immunosorbent assay kit for immunoglobulin G, and the histological presence of H. pylori was identified using the Giemsa stain.
Of the 174 patients, 111 patients (63.8%) were confirmed for H. pylori infection. H. pylori status did not correlate with the overall or disease-free survival. For patients with stage III or IV gastric cancer, a positive H. pylori status was a significant predictive factor for recurrence over that of a negative H. pylori status (P = 0.019). Negative H. pylori status was a predictive factor for recurrence in multivariable analysis (relative risk, 2.724; 95 confidence interval, 1.192 to 6.228).
Helicobacter pylori status did not correlate with the clinicopathologic factors of gastric adenocarcinoma. However, a negative Helicobacter pylori status may be a predictive factor for recurrence in patients diagnosed with advanced gastric adenocarcinoma.
Helicobacter pylori; Stomach neoplasm; Prognosis; Survival
Laparoscopic gastrectomy is a widely accepted surgical technique. Recently, robotic gastrectomy has been developed, as an alternative minimally invasive surgical technique. This study aimed to evaluate the question of whether robotic gastrectomy is feasible and safe for the treatment of gastric cancer, due to its learning curve.
Materials and Methods
We retrospectively reviewed the prospectively collected data of 100 consecutive robotic gastrectomy patients, from November 2008 to March 2011, and compared them to 282 conventional laparoscopy patients during the same period. The robotic gastrectomy patients were divided into 20 initial cases; and all subsequent cases; and we compared the clinicopathological features, operating times, and surgical outcomes between the three groups.
The initial 20 robotic gastrectomy cases were defined as the initial group, due to the learning curve. The initial group had a longer average operating time (242.25±74.54 minutes vs. 192.56±39.56 minutes, P>0.001), and hospital stay (14.40±24.93 days vs. 8.66±5.39 days, P=0.001) than the experienced group. The length of hospital stay was no different between the experienced group, and the laproscopic gastrectomy group (8.66±5.39 days vs. 8.11±4.10 days, P=0.001). The average blood loss was significantly less for the robotic gastrectomy groups, than for the laparoscopic gastrectomy group (93.25±84.59 ml vs. 173.45±145.19 ml, P<0.001), but the complication rates were no different.
Our study shows that robotic gastrectomy is a safe and feasible procedure, especially after the 20 initial cases, and provides a satisfactory postoperative outcome.
Robotic; Laparoscopy; Compared; Gastrectomy; Learning curve
Composite neuroendocrine-exocrine carcinomas are malignancies that have two distinct components residing within the same tumor: an adenocarcinomatous portion and a neuroendocrine portion. This is rare in gastric cancers; however, poorly differentiated adenocarcinomas can sometimes reveal evidence of neuroendocrine features (NEF) or be 'mixed endocrine and exocrine carcinomas'. This study aimed to review NEF in gastric adenocarcinoma and to evaluate its prognostic significance.
Materials and Methods
We selected 29 patients who were diagnosed with gastric adenocarcinoma with NEF and received gastrectomies at the Department of Surgery, Ajou University Hospital between January 2001 and December 2009. We analyzed the clinicopathologic features of gastric cancer with NEF and the prognosis associated with such tumors.
The pathologic result with respect to TNM staging of the gastric cancers with NEF were as follows: 5 cases of T1, 5 cases of T2, 10 cases of T3, and 9 cases of T4. There were 7 cases of N0, 7 cases of N1, 8 cases of N2 and 7 cases of N3. The staging of patients with NEF was higher than that of patients without NEF. Especially tumor lymphovascular invasion rate was 82.8%. The overall survival of patients with gastric cancer characterized by NEF was 73.8 months.
Positive NEF status might be correlated with clinicopathologic parameters such as a high stage and high frequency of regional lymph node metastasis.
Stomach neoplasms; Adenocarcinoma; Neuroendocine tumors
As the proportion of early gastric cancer (EGC) has recently been increased, minimally invasive treatment is currently accepted as main therapy for EGC. Accurate preoperative staging is very important in determining treatment options. To know the accuracy of endoscopic ultrasonography (EUS), we compared the depth of invasion of the tumor with preoperative EUS and postoperative pathologic findings.
Materials and Methods
We retrospectively analyzed 152 patients who underwent EUS before laparoscopic gastrectomy. The preoperative EUS results were compared with the pathological findings.
The overall proportion of coincidence for depth of invasion between EUS and pathologic results was 41.4%. Univariate analysis showed that the rate of corrected prediction of EUS for tumor depth significantly decreased for the lesions more than 3cm in diameter (P=0.033), and those with a depressed morphology (P=0.035). In multivariate analysis, the depressed type (P=0.029, OR=2.873) and upper lesion (P=0.035, OR=2.151) was the significantly independent factors influencing the inaccurate prediction of EUS for tumor depth.
When we decide the treatment modality considering the clinical depth of invasion by EUS, the possibility of discordance with pathologic results should be considered for the lesions located in the upper third of the stomach and with a depressed morphology.
Stomach neoplasms; Endosonography; Neoplasm invasiveness
Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection.
Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection.
The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori.
H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.
Helicobacter pylori; TGF-β; Inflammation; Ulcer; Host defense
The levels of organic acids representing metabolic pathway end products are important indicators of physiological status, and may be associated with metabolic changes in cancer. The aim of this study is to investigate the levels of organic acids in cancerous and normal tissues from gastric cancer patients and to confirm the role of metabolic alterations in gastric carcinogenesis. Organic acids in normal and cancerous tissues from forty-five patients with gastric adenocarcinoma were investigated by gas chromatography-mass spectrometry in selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We analysed the significant differences in the levels of organic acids in normal and cancer tissues and investigated the correlation of these levels in cancer tissues with clinicopathological features. The levels of Krebs cycle components, including α-ketoglutaric acid, succinic acid, fumaric acid, malic acid and oxaloacetic acid, were significantly increased in cancer tissues compared to normal tissues. In addition, the levels of glycolytic products, including pyruvic acid and lactic acid, as well as the levels of ketone bodies, including 3-hydroxybutyric acid, were also significantly increased in cancer tissues compared to normal tissues. The levels of ketone bodies in cancer tissues with differentiated histology and in intestinal-type cancer tissues were significantly increased. The organic acid profiling analysis described here may be a generally useful clinical tool for understanding the complexity of metabolic events in gastric adenocarcinoma, and organic acids may have potential as metabolic markers for the future discovery of diagnostic and therapeutic modalities.
Extended systemic lymphadenectomy (D2) is standard procedure for surgical treatment of advanced gastric cancer (AGC) although less extensive lymphadenectomy (D1) can be applied to early gastric cancer. Complete D2 lymphadenectomy is the mandatory procedure for studies that evaluate surgical treatment results of AGC. However, the actual extent of D2 lymphadenectomy varies among surgeons because of a lacking consensus on the anatomical definition of each lymph node station. This study is aimed to develop a consensus for D2 lymphadenectomy and also to qualify surgeons that can perform both laparoscopic and open D2 gastrectomy.
This (KLASS-02-QC) is a prospective, observational, multicenter study to qualify the surgeons that will participate in the KLASS-02-RCT, which is a prospective, randomized, clinical trial comparing laparoscopic and open gastrectomy for AGC. Surgeons and reviewers participating in the study will be required to complete a questionnaire detailing their professional experience and specific gastrectomy surgical background/training, and the gastrectomy metrics of their primary hospitals. All surgeons must submit three laparoscopic and three open D2 gastrectomy videos, respectively. Each video will be allocated to five peer reviewers; thus each surgeon’s operations will be assessed by a total of 30 reviews. Based on blinded assessment of unedited videos by experts’ review, a separate review evaluation committee will decide whether or not the evaluated surgeon will participate in the KLASS-02-RCT. The primary outcome measure is each surgeon’s proficiency, as assessed by the reviewers based on evaluation criteria for completeness of D2 lymphadenectomy.
We believe that our study for standardization of D2 lymphadenectomy and surgical quality control (KLASS-02-QC) will guarantee successful implementation of the subsequent KLASS-02-RCT study. After making consensus on D2 lymphadenectomy, we developed evaluation criteria for completeness of D2 lymphadenectomy. We also developed a unique surgical standardization and quality control system that consists of recording unedited surgical videos, and expert review according to evaluation criteria for completeness of D2 lymphadenectomy. We hope our systematic approach will set a milestone in surgical standardization that is essential for surgical clinical trials. Additionally, our methods will serve as a novel system for educating surgeons and assessing surgical proficiency.
Neoplasms of stomach; D2 lymphadenectomy; Gastrectomy; Laparoscopy; Standardization; Quality control
The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery.
Materials and Methods
We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates.
Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081).
Peritoneal washing cytology using samples harvested from two different sites in the abdominal cavity was not able to predict peritoneal recurrence or survival in gastric cancer patients. Further studies will be required to determine whether peritoneal washing cytology during gastric cancer surgery is a meaningful procedure.
Stomach neoplasms; Cytology; Peritoneum; Recurrence
The aim of this study is to investigate the clinical factors affecting on the cure rate by invasive and open surgery for gastric cancer and to establish a subgroup of patients who can be applied by the early recovery after surgery program through this retrospective analysis.
Materials and Methods
In this retrospective study, we analyzed 425 patients who underwent gastric cancer surgery between January 2011 and December 2011 and were managed with conventional clinical therapies. This clinical algorithm was made when the patient was in minimally invasive surgery group and discharged from hospital one day faster than them in open surgery group.
The completion rate of the clinical pathway was 62.4%. Despite the different applications of clinical pathway, completion rate in minimally invasive surgery group was significantly higher than that of open group (P<0.001). In multivariate analysis, the surgical procedure of minimally invasive surgery (odds ratio=4.281) was the most predictable factor to complete clinical pathway. Additionally, younger patients (odds ratio=1.933) who underwent distal gastrectomy (odds ratio=1.999) without combined resection (odds ratio=3.069) were predicted to accomplish the clinical pathway without any modifications.
We concluded that high efficacy of the clinical pathway for gastric cancer surgery was expected to selected patients through retrospective analysis (expected completion rate=85.4%). In addition, these patients would become enrolled criteria for early recovery program in gastric cancer surgery.
Stomach neoplasms; Critical pathways; Gastrectomy; Minimally invasive
A randomized controlled trial to evaluate the long-term outcomes of laparoscopic distal gastrectomy for gastric cancer is currently ongoing in Korea. Patients with cT1N0M0-cT2aN0M0 (American Joint Committee on Cancer, 6th edition) distal gastric cancer were randomized to receive either laparoscopic or open distal gastrectomy. For surgical quality control, the surgeons participating in this trial had to have performed at least 50 cases each of laparoscopy-assisted distal gastrectomy and open distal gastrectomy and their institutions should have performed more than 80 cases each of both procedures each year. Fifteen surgeons from 12 institutions recruited 1,415 patients. The primary endpoint is overall survival. The secondary endpoints are disease-free survival, morbidity, mortality, quality of life, inflammatory and immune responses, and cost-effectiveness (ClinicalTrials.gov ID: NCT00452751).
Gastric cancer; Laparoscopy distal gastrectomy; Open distal gastrectomy; Randomized controlled trial
Gastric signet ring cell carcinoma (GSRC) is known to have low fluorodeoxyglucose (FDG) uptake. The aim of the study was to investigate the relation between FDG uptake and glucose transporter (GLUT)-1 expression and clinicopathologic parameters in cases of GSRC.
Materials and Methods
Forty patients (28 men, mean age 54 ± 12 years) with histologically confirmed GSRC who underwent pre-operative [18F]FDG PET/CT were enrolled. Maximum standardized uptake values (SUVmax) were compared with clinicopathologic parameters and GLUT-1 expression. Cases were divided based on GLUT-1 expression in tumor tissues into a membranous group (n = 17) and a cytoplasmic group (n = 23).
Mean SUVmax was significantly higher in the membranous group than in the cytoplasmic group (6.06 ± 2.79 vs. 3.67 ± 1.54, P = 0.03). Gastric wall invasion, depth of invasion, extent of LN metastasis, overall stage, and tumor size were found to be related to SUVmax. On the other hand, age, sex, and the presence of distant metastasis were not related to SUVmax. Multivariate analysis revealed that membranous GLUT-1 expression and the extent of LN metastasis independently predicted high FDG uptake.
This study demonstrates that high FDG uptake is mediated by membranous GLUT-1 expression in GSRC.
Signet ring cell; Stomach cancer; FDG; Glucose transporter-1
The Roux en Y method has rarely been performed due to longer operation time and high risk of complication, despite several merits including prevention of bile reflux. We conducted a retrospective review of the result of Roux en Y reconstruction using two circular staplers after subtotal gastrectomy.
Materials and Methods
From December 2008 to May 2009, a total of 26 patients underwent Roux en Y reconstruction using two circular staplers after subtotal gastrectomy, and seventy-two patients underwent Billroth-I reconstruction. Roux en Y anastomosis was performed using two circular staplers without hand sewing anastomosis. We compared clinicopathologic features and surgical outcomes between the two groups. All patients underwent gastrofiberscopy between six and twelve months after surgery to compare the bile reflux.
No significant differences in clinicopathologic findings were observed between the two groups, except for the rate of minimal invasive surgery (P=0.004) and cancer stage (P=0.002). No differences in the rate of morbidity (P=0.353) and admission duration (P=0.391) were observed between the two groups. Gastrofiberscopic findings showed a significant reduction of bile reflux in the remnant stomach in the Roux en Y group (P=0.019).
When compared with Billroth-I reconstruction, Roux en Y reconstruction using the double stapler technique was found to reduce bile reflux in the remnant stomach without increasing postoperative morbidity. Based on these results, we planned to begin a randomized controlled clinical trial for comparison of Roux en Y reconstruction using this method with Billroth-I anastomosis.
Stomach neoplasms; Gastrectomy; Reconstructive surgical procedure
A 48 year old woman was diagnosed with a huge cystic mass in her abdominal cavity. She complained of significant abdominal discomfort due to the mass. The abdominal computed tomography revealed a giant multi-lobulated mass, measuring 26×12 cm in size, adjacent to the lesser curvature of the stomach. In the operation field, the mass was found to originate from the lesser omentum, including the right and left gastric vessels and the vagus nerves, and to invade the lesser curvature of the stomach. For curative resection, distal subtotal gastrectomy with mass excision followed by gastroduodenostomy were performed. This mass was pathologically diagnosed to be a mesenteric cystic lymphangioma; in fact, the largest ever reported. The patient had no complications during the postoperative period and was discharged from the hospital on the seventh day after surgery.
Lymphangioma; Gastrectomy; Omentum
Incidence of gastroesophageal reflux disease (GERD) is high. antireflux surgery with specific indications could be an option. Nissen fundoplication is the most popular surgical procedure for GERD, and recent results using laparoscopy have reported excellent short- and mid-term results. Regarding surgical outcome of antireflux surgery, the rate of complications has been reported as below 2.4%, but rare cases still require reoperation.
PRESENTATION OF CASE
A 53-year old male patient underwent laparoscopic Nissen fundoplication three years ago owing to gastroesophageal reflux disease (GERD) troubled by dysphagia and heartburn However, despite undergoing surgery, his symptoms did not show improvement .A robotic redo fundoplication was planned. The patient recovered uneventfully, and the esophagography on postoperative day four revealed improvement of previous upward contrast reflux and distension of the distal esophagus during swallowing had disappeared. Dysphagia and heartburn had still not occurred at one year follow-up.
Redo antireflux surgery for postoperative stricture is not an easy procedure due to postoperative adhesion and anatomical change. Robotic surgery may be more helpful for precise dissection of the adhesion site by a previous operation and robotic suturing for re-fundoplication was more effective.
Re-do fundoplication using a robot, which is a complicated procedure compared with primary anti-reflux surgery would be a general procedure in the near future.
Gastroesophageal reflux disease; Redo fundoplication; Robotic surgery
Gastric cancer surgery is a common operation in East Asia, such as Korea and Japan, and there has been a significant increase in the need for this procedure due to the aging population. As a result, surgery for the treatment of gastric cancer for elderly patients is expected to increase. This study examined the effect of old age on gastric cancer surgery, and analyzed the operative risk factors for elderly patients.
Materials and Methods
From November 2008 to August 2010, 590 patients, who underwent a curative resection for gastric cancers, were enrolled. Patients who underwent palliative or emergency surgery were excluded. A retrospective analysis of the correlation between surgical outcomes and age was performed. The elderly were defined as patients who were over the age of 65 years.
The mean age of all patients was 58.3 years, and complications occurred in 87 cases (14.7%). The most common complication was wound infection and severe complications requiring surgical, endoscopic, or radiologic intervention developed in 52 cases (8.8%). The rate of complications increased with increasing age of the patients. Univariate analysis revealed age, comorbidity, extent of resection, operation time, and combined resection to be associated with surgical complications. In particular, age over 75 years old, operation time, and comorbidity were predictive factors in multivariate analysis. In the elderly, only comorbidity was associated with surgical complications.
The patients' age is the most important factor for predicting surgical complications. Surgeons should pay an attention to the performance of gastric cancer surgery on elderly patients. In particular, it must be performed carefully for elderly patients with a comorbidity.
Stomach neoplasms; Risk factors; Gastrectomy; Aged
Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.
arrestin; gene expression profiling; oligonucleotide array sequence analysis; proto-oncogene proteins c-fos; retinal degeneration; transducin
Understanding the molecular pathways mediating neuronal function in retinas can be greatly
facilitated by the identification of genes regulated in the retinas of different mutants under
various light conditions. We attempted to conduct a gene chip analysis study on the genes
regulated during rhodopsin kinase (Rhok−/−) and arrestin (Sag−/−) knockout and double knockouts in mice retina. Hence, mice were exposed to constant illumination of 450 lux or 6,000 lux on dilated pupils for indicated periods. The retinas were removed after the exposure and processed for microarray analysis. Double knockout was associated with immense changes in gene expression regulating a number of apoptosis inducing transcription factors. Subsequently, network analysis revealed that during early exposure the transcription factors, p53, c-MYC, c-FOS, JUN, and, in late phase, NFκB, appeared to be essential for the initiation of light-induced retinal rod loss, and some other classical pro- and antipoptotic genes appeared to be significantly important as well.