ABSTRACT
Purpose@#This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. @*Materials and Methods@#Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. @*Results@#After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. @*Conclusion@#Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.
ABSTRACT
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
ABSTRACT
Purpose@#This study aims to identify the relationship between nursing students’ social anxiety and communication ability, and in particular, to determine the mediating effect of self-efficacy. @*Methods@#A total of 187 nursing students enrolled at four universities in Korea completed surveys between August and September 2020. The measurements included the Global Interpersonal Communication Competence Scale, self-efficacy scales, and interaction anxiousness scales. Data were analyzed using descriptive statistics, an independent t-test, one-way ANOVA, Pearson’s correlation, multiple regression following the Baron and Kenny method, and bootstrapping for mediation. @*Results@#Communication ability was significantly negatively correlated with social anxiety (r=-.61, p<.001) and significantly positively correlated with self-efficacy (r=.77, p<.001). Furthermore, self-efficacy had a partial mediating effect on the relationship between social anxiety and communication ability. @*Conclusion@#The findings of this study suggest that communication ability can be improved if individual characteristics such as social anxiety and self-efficacy are considered. Therefore, when developing communication ability improvement programs for nursing students in the future, it is considered important to actively consider these personal characteristics.
ABSTRACT
Purpose@#A safe and effective hemostatic care is necessary after bone marrow examination to minimize bleeding, pain, and discomfort. However, a standardized hemostatic care protocol following bone marrow examination has not been established. The purpose of this study was to investigate the differences in bleeding, hematoma, pain, and discomfort by the hemostatic method used following bone marrow examination. @*Methods@#This study was carried out with a pre-test/post-test nonequivalent control group design. Sixty-four patients undergoing bone marrow examination at the hemato-oncology ward in a tertiary hospital in South Korea were assigned to an intervention (n = 30) and comparison group (n = 34). The intervention group was treated using a compression dressing alone, while the comparison group received a compression dressing followed by sandbag compression. Both groups received two hours of bedrest. Bleeding, hematoma, pain, and discomfort were measured at one and two hours after the biopsy. @*Results@#No significant differences in the occurrence of bleeding between the groups at one and two hours after bone marrow examination were observed, and no participant developed hematoma. The intervention group had significantly lower pain than the comparison group two hours after the bone marrow examination as well as lower discomfort one hour and two hours after the bone marrow examination (p < .05). @*Conclusion@#Applying only compression dressing after a bone marrow examination is effective in reducing pain and discomfort without measurable differences in bleeding and hematoma, suggesting that compression dressings alone could be effective in lowering pain and discomfort following bone marrow examination.
ABSTRACT
Purpose@#This study aims to identify the relationship between nursing students’ social anxiety and communication ability, and in particular, to determine the mediating effect of self-efficacy. @*Methods@#A total of 187 nursing students enrolled at four universities in Korea completed surveys between August and September 2020. The measurements included the Global Interpersonal Communication Competence Scale, self-efficacy scales, and interaction anxiousness scales. Data were analyzed using descriptive statistics, an independent t-test, one-way ANOVA, Pearson’s correlation, multiple regression following the Baron and Kenny method, and bootstrapping for mediation. @*Results@#Communication ability was significantly negatively correlated with social anxiety (r=-.61, p<.001) and significantly positively correlated with self-efficacy (r=.77, p<.001). Furthermore, self-efficacy had a partial mediating effect on the relationship between social anxiety and communication ability. @*Conclusion@#The findings of this study suggest that communication ability can be improved if individual characteristics such as social anxiety and self-efficacy are considered. Therefore, when developing communication ability improvement programs for nursing students in the future, it is considered important to actively consider these personal characteristics.
ABSTRACT
Purpose@#A safe and effective hemostatic care is necessary after bone marrow examination to minimize bleeding, pain, and discomfort. However, a standardized hemostatic care protocol following bone marrow examination has not been established. The purpose of this study was to investigate the differences in bleeding, hematoma, pain, and discomfort by the hemostatic method used following bone marrow examination. @*Methods@#This study was carried out with a pre-test/post-test nonequivalent control group design. Sixty-four patients undergoing bone marrow examination at the hemato-oncology ward in a tertiary hospital in South Korea were assigned to an intervention (n = 30) and comparison group (n = 34). The intervention group was treated using a compression dressing alone, while the comparison group received a compression dressing followed by sandbag compression. Both groups received two hours of bedrest. Bleeding, hematoma, pain, and discomfort were measured at one and two hours after the biopsy. @*Results@#No significant differences in the occurrence of bleeding between the groups at one and two hours after bone marrow examination were observed, and no participant developed hematoma. The intervention group had significantly lower pain than the comparison group two hours after the bone marrow examination as well as lower discomfort one hour and two hours after the bone marrow examination (p < .05). @*Conclusion@#Applying only compression dressing after a bone marrow examination is effective in reducing pain and discomfort without measurable differences in bleeding and hematoma, suggesting that compression dressings alone could be effective in lowering pain and discomfort following bone marrow examination.
ABSTRACT
Cyclic adenosine monophosphate (cAMP) signaling is critical for regulating metabolic homeostasis in mammals. In particular, transcriptional regulation by cAMP response element-binding protein (CREB) and its coactivator, CREB-regulated transcription coactivator (CRTC), is essential for controlling the expression of critical enzymes in the metabolic process, leading to more chronic changes in metabolic flux. Among the CRTC isoforms, CRTC2 is predominantly expressed in peripheral tissues and has been shown to be associated with various metabolic pathways in tissue-specific manners. While initial reports showed the physiological role of CRTC2 in regulating gluconeogenesis in the liver, recent studies have further delineated the role of this transcriptional coactivator in the regulation of glucose and lipid metabolism in various tissues, including the liver, pancreatic islets, endocrine tissues of the small intestines, and adipose tissues. In this review, we discuss recent studies that have utilized knockout mouse models to delineate the role of CRTC2 in the regulation of metabolic homeostasis.
ABSTRACT
Purpose@#This study aimed to determine whether the diagnosis, treatment approach, and prognosis of multiple myeloma (MM) vary according to the presence and type of disability. @*Materials and Methods@#Demographic, socioeconomic, and medical data were obtained from the National Disability Database, the Korean Central Cancer Registry, and the Korean National Health Insurance claims database. An age- and sex-matched cohort was established using a 1:3 ratio constituted with 2,776,450 people with disabilities and 8,329,350 people without disabilities. Adult patients diagnosed with MM were subsequently selected from this cohort. Disabilities were categorized as physical, communication, intellectual or psychological, and affecting the major internal organs. @*Results@#The cohort included 4,090 patients with MM, with a significantly lower rate per 100,000 persons among people with disabilities than among people without disabilities (29.1 vs. 39.4, p < 0.001). People with disabilities were more likely to undergo dialysis treatment at the time of diagnosis (16.3% vs. 10.0%, p < 0.001), but were less likely to undergo autologous stem cell transplantation (37.5% vs. 43.7%, p=0.072). This trend was more evident among patients with intellectual or psychological disabilities. The median overall survival among patients with disabilities was significantly shorter than that among patients without disabilities (36.8 months vs. 51.2 months, p < 0.001). @*Conclusion@#In Korea, people with disabilities generally have a lower rate of MM diagnosis, receive less intensive treatment, and have a lower survival rate than people without disabilities.
ABSTRACT
PURPOSE: Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL. RESULTS: Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015). CONCLUSION: Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.
Subject(s)
Humans , Antiemetics , Dexamethasone , Drug Therapy , Nausea , Quality of Life , VomitingABSTRACT
PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.
Subject(s)
Humans , Ascites , Biomarkers , Carcinoembryonic Antigen , Carcinoma , Cohort Studies , Diagnosis , Down-Regulation , Exosomes , Liver , MicroRNAs , Prognosis , RNA , Stomach NeoplasmsABSTRACT
PURPOSE: Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. MATERIALS AND METHODS: Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI-treated patients were analyzed retrospectively. RESULTS: EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026). CONCLUSION: EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.
Subject(s)
Humans , Adenocarcinoma , Constriction , Diagnosis , Disease-Free Survival , Lung Neoplasms , Lung , Pleural Effusion , Pleural Effusion, Malignant , Protein-Tyrosine Kinases , ErbB Receptors , Retrospective Studies , TyrosineABSTRACT
BACKGROUND/AIMS: The purpose of the present study was to assess the prevalence of and factors associated with anxiety and depression in Korean patients with advanced gastrointestinal cancer. METHODS: One hundred and twenty consecutive patients with newly diagnosed, advanced gastrointestinal cancer who were scheduled to receive palliative chemotherapy between July 2012 and June 2014 were enrolled in this observational prospective study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-9 (PHQ-9). RESULTS: Thirty-seven patients (30.8%) had anxiety or depression with clinical significance according to HADS or PHQ-9. Multivariate analysis identified lower performance status (odds ratio [OR], 4.19; 95% confidence interval [CI], 1.22 to 14.35; p = 0.023), gastric cancer (OR, 5.39; 95% CI, 0.37 to 78.23; p = 0.018), and knowledge of advanced cancer (OR, 15.07; 95% CI, 1.80 to 125.90; p = 0.012) as significantly associated with anxiety or depression. Twenty-one patients with anxiety or depression visited the psycho-oncologic clinic. In these patients, PHQ-9 score (p = 0.008), global health status (p = 0.023), fatigue (p = 0.047), and appetite loss (p = 0.006) improved from baseline to 3 months after study enrollment. CONCLUSIONS: Approximately 30% of Korean patients with advanced gastrointestinal cancer had anxiety or depression. The prevalence of anxiety or depression was higher in patients with poor performance status, gastric cancer, or knowledge of advanced cancer. Psychiatric interventions may be effective in reducing depression and improving quality of life in cancer patients with anxiety or depression.
Subject(s)
Humans , Anxiety , Appetite , Depression , Drug Therapy , Fatigue , Gastrointestinal Neoplasms , Global Health , Multivariate Analysis , Prevalence , Prospective Studies , Quality of Life , Stomach NeoplasmsABSTRACT
We report a rare case of long-term survival in a patient who received local therapy and salvage chemotherapy for recurrent metastases, along with a literature review. A 65-year-old male patient underwent subtotal gastrectomy for advanced gastric adenocarcinoma. Six months after gastrectomy, 2 metastatic intra-abdominal lymph node enlargements were detected, which were treated with radiotherapy. At 55 months after gastrectomy, an abdominal wall mass was detected, which was treated by surgical resection. The patient received 5-fluorouracil/leucovorin/irinotecan chemotherapy for 27 months before and after radiotherapy and docetaxel chemotherapy for 6 months after surgical resection of the abdominal wall metastasis. At the last visit, 7.8 years since the initial resection of the primary gastric cancer and 6.2 years since detection of the first metastases, the patient was disease-free and required no further chemotherapy. This case suggests that repeated local therapy offers potential for long-term survival in a carefully selected subset of patients with recurrent metastases.
Subject(s)
Aged , Humans , Male , Abdominal Wall , Adenocarcinoma , Drug Therapy , Gastrectomy , Lymph Nodes , Neoplasm Metastasis , Radiotherapy , Stomach NeoplasmsABSTRACT
PURPOSE: This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen. MATERIALS AND METHODS: Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m² intravenously (IV) on D1 (D), docetaxel 60 mg/m² IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m2 IV D1 plus oral S-1 30 mg/m² twice a day on D1-14 (DS). RESULTS: Seventy-two patients were randomized to the D (n=23), DC (n=24), or DS (n=25) group. The confirmed response rate was 4.3% (95% confidence interval [CI], 0% to 12.6%), 4.3% (95% CI, 0% to 12.6%), and 8.7% (95% CI, 0% to 20.2%) for the D, DC, and DS groups, respectively. Compared to the D arm, the DS arm had a better progression-free survival (2.7 months vs. 1.3 months, p=0.034) without any deterioration in safety or quality of life, whereas the DC arm had a similar progression-free survival (1.8 months vs. 1.3 months, p=0.804) and poorer overall survival (5.6 months vs. 10.0 months, p=0.035). CONCLUSION: A re-challenge with S-1, but not cisplatin, in combination with docetaxel has potential anticancer benefits over docetaxel alone in MGC with progression after prior cisplatin plus S-1 or capecitabine.
Subject(s)
Humans , Antineoplastic Agents , Arm , Capecitabine , Cisplatin , Disease-Free Survival , Drug Therapy , Quality of Life , Stomach NeoplasmsABSTRACT
PURPOSE: Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. MATERIALS AND METHODS: Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. RESULTS: Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). CONCLUSION: We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.
Subject(s)
Humans , Antiemetics , Blood Glucose , Dexamethasone , Diabetes Mellitus , Diagnosis , Drug Therapy , Fasting , Gastrointestinal Neoplasms , Glucose , Homeostasis , Incidence , Insulin , Insulin Resistance , Multivariate Analysis , Nausea , Pilot Projects , VomitingABSTRACT
PURPOSE: The purpose of the present study was to assess factors associated with quality of life (QOL) and to determine whether anxiety and depression are predictive of QOL in patients with advanced gastrointestinal cancer at initial diagnosis and during the treatment process. METHODS: One hundred and twenty patients with gastrointestinal cancer requiring palliative chemotherapy were enrolled. RESULTS: At baseline, depression, performance status, and anxiety accounted for 55.0% (p<.001) of the variance in global health status score, depression accounted for 22.0% (p<.001) of the variance in functional scales score, and anxiety accounted for 19.0% (p<.001) of the variance in symptom scales score. At 3 months, depression, pain, and performance status accounted for 72.0% (p<.001) of the variance in global health status score, 76.0% (p<.001) of the variance in functional scales score, and 74.0% (p<.001) of the variance in symptom scales score. CONCLUSION: Anxiety and depression were significant predictive factors of QOL in patients with advanced gastrointestinal cancer. Depression and performance status were significant predictive factors of QOL at both baseline and 3 months, and anxiety and pain were significant predictive factors of QOL at baseline and 3 months, respectively.
Subject(s)
Humans , Anxiety , Depression , Diagnosis , Drug Therapy , Gastrointestinal Neoplasms , Global Health , Quality of Life , Weights and MeasuresABSTRACT
Glucose homeostasis is tightly regulated to meet the energy requirements of the vital organs and maintain an individual's health. The liver has a major role in the control of glucose homeostasis by controlling various pathways of glucose metabolism, including glycogenesis, glycogenolysis, glycolysis and gluconeogenesis. Both the acute and chronic regulation of the enzymes involved in the pathways are required for the proper functioning of these complex interwoven systems. Allosteric control by various metabolic intermediates, as well as post-translational modifications of these metabolic enzymes constitute the acute control of these pathways, and the controlled expression of the genes encoding these enzymes is critical in mediating the longer-term regulation of these metabolic pathways. Notably, several key transcription factors are shown to be involved in the control of glucose metabolism including glycolysis and gluconeogenesis in the liver. In this review, we would like to illustrate the current understanding of glucose metabolism, with an emphasis on the transcription factors and their regulators that are involved in the chronic control of glucose homeostasis.
Subject(s)
Gluconeogenesis , Glucose , Glycogenolysis , Glycolysis , Homeostasis , Liver , Metabolic Networks and Pathways , Metabolism , Negotiating , Protein Processing, Post-Translational , Transcription FactorsABSTRACT
Colorectal cancer (CRC) affects largely elderly populations. However, older patients with CRC are generally excluded from randomized clinical trials, and the healthy subjects who are recruited are not representative of the general elderly patient population. Nevertheless, recent data from clinical trials specifically targeting elderly patients and related subgroup analyses indicate that well-selected elderly patients can have a similar response to that of younger patients. Chronological age should not determine the candidacy for adjuvant or palliative chemotherapy in elderly patients with CRC. The appropriate management of healthy elderly patients would mean that they could receive aggressive chemotherapy in a similar regimen to that of younger patients, whereas the care of frail elderly patients and those with a short life expectancy should focus on palliation. The use of a comprehensive geriatric assessment could allow the use of safe and beneficial chemotherapy regimens in elderly patients with CRC.
Subject(s)
Aged , Humans , Colorectal Neoplasms , Drug Therapy , Frail Elderly , Geriatric Assessment , Life ExpectancyABSTRACT
Colorectal cancer (CRC) affects largely elderly populations. However, older patients with CRC are generally excluded from randomized clinical trials, and the healthy subjects who are recruited are not representative of the general elderly patient population. Nevertheless, recent data from clinical trials specifically targeting elderly patients and related subgroup analyses indicate that well-selected elderly patients can have a similar response to that of younger patients. Chronological age should not determine the candidacy for adjuvant or palliative chemotherapy in elderly patients with CRC. The appropriate management of healthy elderly patients would mean that they could receive aggressive chemotherapy in a similar regimen to that of younger patients, whereas the care of frail elderly patients and those with a short life expectancy should focus on palliation. The use of a comprehensive geriatric assessment could allow the use of safe and beneficial chemotherapy regimens in elderly patients with CRC.
Subject(s)
Aged , Humans , Colorectal Neoplasms , Drug Therapy , Frail Elderly , Geriatric Assessment , Life ExpectancyABSTRACT
Glucose homeostasis is tightly controlled by the regulation of glucose production in the liver and glucose uptake into peripheral tissues, such as skeletal muscle and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly responsible for glucose production in the liver, which is essential for tissues, organs, and cells, such as skeletal muscle, the brain, and red blood cells. Hepatic gluconeogenesis is controlled in part by the concerted actions of transcriptional regulators. Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. Protein arginine methyltransferases (PRMTs) were recently added to the list of enzymes that are critical for regulating transcription in hepatic gluconeogenesis. In this review, we briefly discuss general aspects of PRMTs in the control of transcription. More specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of FoxO1- and CREB-dependent transcriptional events.