Association between dynapenia and cognitive decline in community-dwelling older Japanese adults: The IRIDE Cohort Study.

AIM: Muscle mass and strength correlate with cognitive function; however, it remains unclear whether dynapenia (i.e., muscle weakness with preserved muscle mass) is relevant. This study aimed to explore whether dynapenia is associated with global cognitive function in community-dwelling older Japanese adults. METHODS: This cross-sectional study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study, which pooled data from five community-based geriatric cohorts. Dynapenia was defined as muscle weakness without muscle mass loss according to the Asian Working Group for Sarcopenia criteria. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). An ordered logistic regression analysis was conducted with dynapenia as the exposure and with cognitive decline stages, defined as an MMSE score of 27-30 for normal cognition, 24-26 for possible cognitive decline, and <24 for cognitive decline, as the outcome, stratified by sex and adjusted for age, muscle mass, education, alcohol consumption, smoking habits, living alone, and non-communicable diseases. RESULTS: We analyzed data for 3338 participants (2162 female) with preserved muscle mass. Of these, 449 (13.5%) had dynapenia, and 79 (2.4%) exhibited cognitive decline. Multivariate odds ratios (95% confidence interval) for cognitive decline among those with dynapenia, compared with those without dynapenia, were 1.51 (1.02-2.24) for males and 2.08 (1.51-2.86) for females. CONCLUSIONS: Muscle weakness is associated with cognitive decline, even in individuals with preserved muscle mass. Further studies are needed to better understand the association between muscle weakness and cognitive decline over time in order to develop dementia prevention strategies for those with dynapenia. Geriatr Gerontol Int 2024; 24: 123-129.

The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer.

The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62-RBP6 interaction.

The prevalence and clinical implications of pancreatic fat accumulation identified during a medical check-up.

ABSTRACT: Fatty pancreas (FP) is characterized by pancreatic fat accumulation and the subsequent development of pancreatic and metabolic complications. However, FP has not been categorized in the manual for abdominal ultrasound in cancer screening and health check-ups in Japan, and the pathology of FP has not been fully elucidated.Nine hundred and nineteen people who underwent a medical check-up had the severity of their pancreatic fat accumulation categorized after transabdominal ultrasonographic examination. The relationships between FP, lifestyle-related diseases, and fatty liver disease at this time were assessed using stratification analysis.The prevalence of FP was 46.8% (430/919). People with FP were more likely to be male and had higher prevalences of lifestyle-related diseases, including fatty liver disease. Men and women were similarly represented in each tertile of pancreas brightness. Older age; high waist circumference, triglyceride and glucose index, serum low-density lipoprotein-cholesterol, hepatic steatosis index; and low serum amylase were associated with the presence of severe FP. Moreover, the group with severe liver steatosis had a higher prevalence of FP and a higher pancreatic brightness score. Logistic regression analysis showed that individuals with liver steatosis were more likely to have severe FP.The severity of FP is associated with features of lifestyle-related diseases and the severity of liver steatosis. These findings suggest that high visceral fat content is associated with more severe fatty pancreas as a phenotype of ectopic fat accumulation, as well as fatty liver disease.

Relationships of Dietary Habits and Physical Activity Status with Non-Alcoholic Fatty Liver Disease Featuring Advanced Fibrosis.

(1) Aim: Hepatic fibrosis is a prognostic factor for disease progression in non-alcoholic fatty liver disease (NAFLD). We aimed to determine the relationships between diet, physical activity, and the progression of liver fibrosis. (2) Methods: The 349 participants were categorized by their FibroScan-aspartate aminotransferase score, and they completed a questionnaire regarding their diet and physical activity. (3) Results: There were 233 patients in the negative-on-screening group, 78 in the gray zone group, and 38 in the positive-on-screening group. The frequencies of consumption of soybeans and soybean products and of light-colored vegetables were lower in the positive group; whereas the frequencies of consumption of snack food and fried sweets, jelly and pudding, fried food, and butter, lard, and beef tallow were higher. The odds ratios for the fibrosis progression in patients who consumed fried food ≥4 times/week was 2.21. The positive group also showed lower physical activity level (PAL) and exercise (Ex, metabolic equivalents for tasks (METs)/hour/week). The patients who undertook Ex at >7.5 had an odds ratio of 0.21 for the fibrosis progression. (4) Conclusion: High consumption of fried food and low Ex are risk factors for the fibrosis progression in NAFLD.

Phosphorylated mTOR expression as a predictor of survival after liver resection for colorectal liver metastases.

BACKGROUND: Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS: Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS: The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS: mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.

Wisteria floribunda agglutinin-sialylated mucin core polypeptide 1 is a sensitive biomarker for biliary tract carcinoma and intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: Wisteria floribunda agglutinin (WFA)-sialylated mucin core polypeptide 1 (MUC1) was investigated as a new glycoprotein marker for cholangiocarcinoma (CC) using glycoproteomics technologies. In this multicenter study, WFA-sialylated MUC1 levels in serum and bile samples were measured to determine their diagnostic capability in biliary tract carcinoma (BTC) and intrahepatic (Ih) CC. METHODS: The study included 244 patients with BTC, 59 patients with IhCC, 287 patients with benign biliary tract diseases, and 44 control subjects. RESULTS: Serum WFA-sialylated MUC1 levels were significantly higher in patients with either BTC or IhCC than in control subjects and those with benign biliary tract diseases. Patients with IhCC showed higher WFA-sialylated MUC1 levels than patients with tumors at other sites. No significant differences in WFA-sialylated MUC1 levels were found with regard to cancer stage or tissue type. Receiver operating characteristic curve analysis showed that WFA-sialylated MUC1 was superior to carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for the diagnosis of benign biliary tract diseases, BTC, and IhCC, as well as for stage I and II carcinomas. Significantly higher levels of biliary WFA-sialylated MUC1 were observed in BTC/IhCC than in benign biliary tract diseases. The diagnostic capability of biliary WFA-sialylated MUC1 was also superior to that of CA19-9, and diagnostic sensitivity was higher than that of biliary cytology for BTC/IhCC. CONCLUSIONS: WFA-sialylated MUC1 is a useful novel biomarker for BTC/IhCC. In the future, this measurement should be applied in the clinical setting.

Impact of host and histopathological factors on the discrepancies in estrogen receptor, and progesterone receptor, and HER2 status between core needle biopsy and surgically excised tumors.

PURPOSE: The high reliability and utility of core needle biopsy (CNB) have been previously described. Our aim in this study was to clarify the host and histopathological factors influencing the discrepancies in ER, PgR, and HER2 status between CNB and surgically excised tumors (SET). METHODS: All patients diagnosed with operable invasive breast cancer in our hospital between January 2005 and April 2015 were included in the study; patients who required neoadjuvant chemotherapy were excluded. ER, PgR, and HER2 expression were assessed between paired CNB and SET samples. ER and PgR status were determined using immunohistochemistry(IHC). HER2 status was determined using IHC and scored from 0 to 3+. Fluorescence in-situ hybridization analysis was carried out in HER2 2+ cases. The cut off point for ER and PgR positivity was set at 1%. RESULTS: A total of 1307 patients were assessed. The concordance rates of ER, PgR, and HER2 status in CNB and SET were 95%, 84% and 97%, respectively. Factors of discrepancy were nuclear grade, histological type, and menopausal status for ER and PgR, and none detected for HER2. The discrepancy factors were assessed with univariate and multivariate analysis. CONCLUSIONS: Using the largest known dataset to date of paired samples from a single institution, we evaluated the accuracy of CNB and the discrepancy factors between CNB and SET in breast cancer patients. We conclude that CNB for ER and PgR assessment in postmenopausal patients before treatment should be used with caution. Further research will contribute to increased CNB accuracy, improving patient treatment decisions.

[A Case Report of Clinical Complete Response with Chemotherapy for Descending Colon Cancer Complicated with Severe Pulmonary Dysfunction].

A 76-year-old male patient was diagnosed with progressive descending colon cancer. Since the patient had severe respiratoryfunction impairment after right pneumonectomy, the anesthesiologydepartment of our hospital determined that general anesthesia induction was too difficult. He was thus started on capecitabine plus oxaliplatin(XELOX)therapy. Three months after starting this treatment, colonoscopyshowed that the site had become scarred, and tissue examination revealed no indication of malignancy. Accordingly, the patient achieved clinical complete response. The patient had no findings of recurrence 1 year and 11 months after the start of chemotherapy. Chemotherapy for unresectable progressive recurrent colorectal cancer is based on the 5-FU anticancer agent, which exerts its antitumor effect byinhibiting DNA synthesis. The antitumor effect is reportedly high when the expression of thymidylate synthase(TS), a target agent, is low. In this patient, TS expression was low based on tissue examination. TS expression maybe an effective useful predictive factor for the efficacyof chemotherapyadministered to patients with unresectable progressive recurrent colorectal cancer.

Expression of Sex Determining Region Y-Box 2 and Pancreatic and Duodenal Homeobox 1 in Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The World Health Organization 2010 classification divides pancreatic neuroendocrine tumors (p-NETs) entity to well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC) by Ki-67 index. The aim of this study is elucidate the pathophysiology and tumor biology of p-NETs. METHODS: We assessed the expression of transcription factors sex determining region Y-box 2 (SOX2) and pancreatic and duodenal homeobox 1 (Pdx1)) essential for the normal fetal development of pancreatic neuroendocrine cells in 46 surgically resected p-NETs by immunohistochemistry. The relationship of expression levels of these factors and clinicopathological factors were analyzed. RESULTS: SOX2 was positive in 6 p-NETs (13.0%). Five of 7 NEC patients showed positive for SOX2. SOX2 was highly (sensitivity 71%) and specifically (specificity 97%) expressed in NEC. Patients with SOX2 positive p-NET showed the significantly shorter disease-free and overall survival than patients with SOX2 negative p-NET. High Pdx1 expression was seen in 25 p-NET patients (54.3%). None of the NEC patients showed high Pdx1 expression. There was a significant reverse correlation between SOX2 and Pdx1 expression. CONCLUSIONS: The expression patterns of SOX2 and Pdx1 highly correlated with prognosis of p-NETs. These expression patterns may represent the biological and pathophysiological difference of p-NETs and indicate the origin of tumor.

Therapeutic effect of hybrid training of voluntary and electrical muscle contractions in middle-aged obese women with nonalcoholic fatty liver disease: a pilot trial.

BACKGROUND: Exercise training is an effective therapy for nonalcoholic fatty liver disease (NAFLD). Hybrid training (HYB) of voluntary and electrical muscle contractions was developed to prevent disuse atrophy during space flight. HYB can be applied to obtain a strength training effect accompanying articular movement. In this pilot study, we aimed to investigate the therapeutic efficacy of HYB in NAFLD. METHODS: A total of 15 middle-aged obese women with NAFLD who had no improvement in serum alanine aminotransferase levels and/or liver fat deposition after 12 weeks of lifestyle counseling participated in an HYB program. HYB of the quadriceps and hamstrings was conducted for 20 minutes twice a week for 24 weeks. RESULTS: NAFLD patients showed attenuated intramyocellular lipid levels in the quadriceps after the HYB intervention (-15.5%). Levels of leptin (-17.4%), tumor necrosis factor-α (-23.2%), and interleukin-6 (-30.5%) were also decreased after the intervention. HYB led to a significant body weight reduction (-4.7%), which in turn was associated with a significant decrease in serum alanine aminotransferase (-35.8%), gamma-glutamyl transpeptidase (-21.6%), ferritin (-16.0%), oxidative stress (-17.8%) levels, and insulin resistance values (-2.7%). CONCLUSION: In NAFLD, HYB exerts an antiobesity effect and attenuates liver dysfunction and insulin resistance in association with an increase in muscle strength and a decrease in ectopic muscle fat. Therefore, HYB has great potential as a new type of exercise therapy for liver disease in patients with NAFLD.

[A Case of Multiple Liver Metastases and Peritoneal Dissemination after Resection of a Gastrointestinal Stromal Tumor of the Stomach Successfully Treated with Imatinib Mesylate].

A 71-year-old man was diagnosed with a gastric tumor approximately 50mm in diameter on computed tomography (CT). In January 2000, he underwent a proximal gastrectomy. Pathological examination showed 5 mitoses per 50 high-power fields, while immunohistochemical analysis showed positive staining for KIT. Accordingly, the tumor was diagnosed as an intermediate- risk malignant gastrointestinal stromal tumor (GIST) for which the patient was followed. In January 2002, an abdominal CT scan revealed multiple hepatic tumors and a lower abdominal tumor, and the patient was diagnosed with liver metastases and peritoneal disseminations from GIST. After informed consent was provided, chemotherapy with 400 mg/day imatinib was initiated. The patient demonstrated a partial response 2 months after treatment. At 12 years 8 months after the diagnosis of liver metastasis and peritoneal disseminations, the patient shows no sign of recurrence.

[A Case of Idiopathic Thrombocytopenic Purpura during Adjuvant Chemotherapy for Colon Cancer].

A 76-year-old man underwent surgery for sigmoid colon cancer. The pathological finding was stage Ⅱ with a high-risk of recurrence (SI [bladder], l y0, v2, pN0, H0, P0, M0). He was treated with TS-1 as adjuvant chemotherapy. After the 1 course of chemotherapy, his platelet count was 4,000/mL. The high index of platelet associated IgG (PA-IgG) and bone marrow examination suggested that thrombocytopenia was caused by idiopathic thrombocytopenic purpura. The platelet count improved by prednisolone administration and Helicobacter pylori eradication treatment. After 6 months with no administration of adjuvant chemotherapy, the colon cancer recurred locally, and we performed a Hartmann's operation.

[Two Cases of Pancreatic Neuroendocrine Tumor with Liver Metastases Successfully Treated with Multidisciplinary Therapy including Multiple Surgical Resections].

UNLABELLED: We report 2 cases of pancreatic neuroendocrine tumor with liver metastases successfully treated with multidisciplinary therapy, including multiple surgical resections. Case 1: A 63-year-old man underwent distal pancreatectomy and portal vein resection for a pancreatic body tumor. Histological analysis revealed the tumor was a pancreatic neuroendocrine tumor (p-NET), classified as NET G2. His metachronous liver metastases were treated with lateral sectionectomy and 2 rounds of transcatheter arterial chemoembolization (TACE). He is being treated with everolimus for para-aortic lymph node metastases and is alive 90 months after the primary operation. Case 2: A 64-year-old man underwent distal gastrectomy for a duodenal ulcer and distal pancreatectomy for a pancreatic tumor. The histological diagnosis was gastrinoma classified as NET G2. Hepatectomy (segmentectomy of segment 8 and partial hepatectomy) was performed twice for metachronous liver metastases. Everolimus has been administered for liver and para-aortic lymph node metastases, and the patient is alive 108 months after the primary operation. CONCLUSION: Multidisciplinary treatment should be considered for patients with p-NETs with multiple metastases.

Delayed perforation of the sigmoid colon after endoscopic reduction of sigmoid volvulus.

Case: An 81-year-old woman was diagnosed with sigmoid volvulus. As there were no signs of peritoneal irritation, emergency endoscopic reduction was attempted and achieved successfully. Although she remained stable on the following day, she suddenly developed perforative pan-peritonitis 35 h after the procedure. Outcome: Emergency laparotomy revealed a 10-mm-diameter perforation at the anti-mesenteric wall of the top of the sigmoid loop, and sigmoid resection with Hartmann's procedure was carried out. Pathological examination revealed ischemic necrosis around the perforation site. She recovered well with intensive care, and was discharged 32 days later. Conclusion: Delayed sigmoid perforation after endoscopic reduction of sigmoid volvulus is a rare but important and life-threatening pitfall, and should always be considered by acute care physicians. To prevent this dangerous complication, evaluation of the viability of the entire sigmoid by direct vision and semi-emergency operation as soon as the patient's condition is optimized after endoscopic reduction may be essential.

Acceleration training for managing nonalcoholic fatty liver disease: a pilot study.

BACKGROUND: While aerobic training is generally recommended as therapeutic exercise in guidelines, the effectiveness of resistance training has recently been reported in the management of nonalcoholic fatty liver disease (NAFLD). Acceleration training (AT) is a new training method that provides a physical stimulation effect on skeletal muscles by increasing gravitational acceleration with vibration. AT has recently been indicated as a component of medicine. In this study, we evaluated the effectiveness of AT in the management of NAFLD in obese subjects. METHODS: A total of 18 obese patients with NAFLD who had no improvement in liver function test abnormalities and/or steatosis grade after 12 weeks of lifestyle counseling were enrolled in an AT program. These patients attended a 20-minute session of AT twice a week for 12 consecutive weeks. RESULTS: During the AT program, the NAFLD patients showed a modest increase in the strength (+12.6%) and cross-sectional area (+3.1%) of the quadriceps, coupled with a significant reduction in intramyocellular lipids (-26.4%). Notably, they showed a modest reduction in body weight (-1.9%), abdominal visceral fat area (-3.4%), and hepatic fat content (-8.7%), coupled with a significant reduction in levels of aminotransferase (-15.7%), γ-glutamyltransferase (-14.4%), leptin (-9.7%), interleukin-6 (-26.8%), and tumor necrosis factor-α (-17.9%), and a significant increase of adiponectin (+8.7%). On a health-related quality of life survey, the patients showed an improvement in physical functioning (+17.3%), physical role (+9.7%), general health (+22.1), and social functioning (+6.0%). CONCLUSION: AT reduced hepatic and intramyocellular fat contents and ameliorated liver function test abnormalities in obese patients with NAFLD, which was coupled with improved physical function and body adiposity. AT is clinically beneficial for the management of NAFLD.

[A successful case with TS-1+CDDP chemotherapy for recurrent gastric cancer].

A 64-year-old woman underwent cholecystectomy for treatment of cholecystolithiasis in January 2005. Pathological examination rendered a diagnosis of gallbladder carcinoma. Wedge resection of the liver and dissection of the lymph nodes was performed. No tumor cells in either the liver nodule or lymph nodes were found during pathological examination. At 4 years after surgery, paraaortic lymph node recurrence was confirmed by computed tomography (CT). Gemcitabine was administered once weekly for the first 3 weeks in a monthly cycle, but the tumor continued to increase in size. Gemcitabine was then switched to TS-1, after which it was changed to cisplatin because of continued tumor growth. After 35 courses of chemotherapy, CT showed the disappearance of the paraaortic lymph node, and the patient achieved a complete response. She is currently free of disease at 9 years after surgery.

[A case of recurrent gastric cancer successfully treated with TS-1+CDDP chemotherapy].

A 74-year-old woman underwent distal gastrectomy and D1+ α dissection for the treatment of gastric cancer (pT2a, pN2, H0, P0, M0, Stage IIIA) in February 2008. She was treated with adjuvant postoperative chemotherapy consisting of TS-1. However, 32 months after the operation, paraaortic lymph node recurrence was confirmed by computed tomography (CT). She was treated with combined TS-1 and cisplatin chemotherapy. After 14 courses, CT revealed that the paraaortic lymph node metastasis had disappeared, and a complete response was attained. The patient is currently disease-free, 6 years after the operation.

[A case of hepatoid adenocarcinoma of the stomach].

The patient was a 76-year-old man with no chief complaint. He presented to an internist of our hospital for an evaluation of anemia. An upper gastrointestinal endoscopy revealed a type 2 tumor at the lesser curvature of the gastric body. Although the blood analysis showed a high amount of AFP(2, 328 ng/mL), there was no abnormality found in the liver with a CT scan. The tumor was presumed to be an AFP-producing gastric cancer on the basis of the tumor biopsy. We performed total gastrectomy, splenectomy and cholecystectomy. The tumor cells were positive for AFP by immunohistochemistry. The final diagnosis was hepatoid adenocarcinoma, pT3(SS), INF b, ly1, v2, pN1(3/42), pStage II B. Tumor cells were negative for antihepatocyte antibody and anti-HER2 antibody. The amount of AFP normalized postoperatively. After discharge, he was treated with S-1(80mg/day)orally. He is relapse-free now, 14 months after the operation. Hepatoid adenocarcinoma is an extremely aggressive tumor with a poor prognosis, and effective chemotherapy has still not been established. A larger number of analyses, along with a molecular biological approach, is sure to be helpful for the establishment of an effective treatment for hepatoid adenocarcinoma.

Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma.

BACKGROUND: Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC. METHODS: We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of FGF19 and FGFR4 to regulate their concentrations. RESULTS: We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (P < 0.05). Univariate and multivariate analyses revealed that the tumor FGF19 mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (P < 0.01, n = 12) and invasion (P < 0.01, n = 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (P < 0.01, n = 12). Inversely, decreasing FGF19 and FGFR4 expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (P < 0.01, n = 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (P < 0.01, n = 29). CONCLUSIONS: FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.

CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer.

Interaction between CXCR4 and CXCL12 plays a role in tumor progression. The present study examined CXCR4, CXCL12 and CD133 expression in liver metastases of colorectal cancer (CLM) and determined whether the expression profiles affect the tumor microenvironment and thus progression, and whether they could serve as a prognostic marker for survival. Liver metastases of colorectal cancer collected from 92 patients were evaluated by CXCR4, CXCL12 and CD133 immunohistochemistry and clinicopathological data were analyzed. The expression profile of CXCR4 was determined in the colorectal cancer cell line, SW48. The expression of cytoplasmic CXCR4 was higher in 36 (39%) patients than that indicated by CXCR4 staining intensity of hepatocytes. High levels of nuclear CXCR4 expression in 23 (25%) patients significantly correlated with CXCL12 expression in hepatocytes. Nuclear CXCR4 expression was increased in the cancer cells after exposure to CXCL12. Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM. The expression of CXCR4 and CXCL12 in CLM may have an interactive effect that could alter the tumor microenvironment. CXCR4 expression in metastatic liver tumors together with the upregulation of CXCL12 in hepatocytes may help to predict the clinical outcomes of patients with CLM after hepatectomy.