AIM: To evaluate the prevalence and predictive factors of osteoporosis in patients with gastric adenocarcinoma alter gastrectomy.METHODS: The study included 133 patients diagnosed with gastric adenocarcinoma but who...AIM: To evaluate the prevalence and predictive factors of osteoporosis in patients with gastric adenocarcinoma alter gastrectomy.METHODS: The study included 133 patients diagnosed with gastric adenocarcinoma but who did not undergo prior diagnostic work-up for osteoporosis. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and vertebral deformity was assessed by plain X-rays. We evaluated the effects of age, sex, body mass index (BMI), anemia, back pain, vertebral deformity, tumor staging, reconstruction type, and past medical history to determine predictive factors of osteoporosis in these patients.RESULTS: The prevalence of osteoporosis in the lumbar spine was 38.3% (male, 28.9%; female, 54.0%), and 15.0% in the femoral neck (male, 10.8%; female, 22.0%). The vertebral deformity rate was 46.6% (male, 43.4%; female, 52.0%). Age, BMI and hemoglobin correlated with BMD (P 〈 0.01). In males, anemia and age 〉 64 years were independent predictive factors of osteoporosis in multivariate analysis. In females, back pain was an independent factor for osteoporosis.CONCLUSION: The results of this study revealed that prevalence of osteoporosis and vertebral bone deformity rate were high in gastric cancer patients, regardless of post-gastrectomy duration and operation type. Early diagnosis and a proper management plan must be established in these patients.展开更多
BACKGROUND Extrahepatic metastasis(EHM)from hepatocellular carcinoma(HCC)occurs in 10%–15%of cases following initial treatment.The most frequent sites of EHM are the lung,lymph nodes,and bone.Gastrointestinal or brai...BACKGROUND Extrahepatic metastasis(EHM)from hepatocellular carcinoma(HCC)occurs in 10%–15%of cases following initial treatment.The most frequent sites of EHM are the lung,lymph nodes,and bone.Gastrointestinal or brain metastasis from HCC is rarely reported.Here,we report a rare case of concurrent HCC metastases to the stomach,colon,and brain.CASE SUMMARY A 72-year-old male with a history of alcohol induced HCC presented with multiple intrahepatic recurrences and tumorous lesions in the stomach and ascending colon.Three years earlier,he underwent right hemihepatectomy,and 1 year ago,he had a video-assisted thoracoscopic wedge resection for pulmonary metastasis of HCC.We decided on surgical resection of the new metastases because of massive gastric bleeding and concern for possible colonic obstruction.The patient underwent gastric wedge resection and right hemicolectomy.Two weeks later,the patient developed dysarthria and mild cognitive disorder.Magnetic resonance imaging of the brain revealed a left frontal lobe lesion,and he underwent resection of a metastatic brain tumor.Unfortunately,he died 6 weeks after the last surgery due to hepatorenal syndrome.CONCLUSION Decision of surgery was carefully recommended in this case and may extend survival in other metastatic HCC patients with well-preserved hepatic function.展开更多
Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This ...Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates EMT.Methods: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging system.Results: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner. Pharmacological inhibition of this axis via CAMKK2inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KLcancer cells in vivo.Conclusions: This study demonstrates that autophagy-derived acetyl-CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRASLKB1 co-mutated lung cancer cells and that inhibition of the autophagy/acetylCoA/acetyl-Snail axis using CAMKK2 or ACLY inhibitors could be a potentialtherapeutic strategy to suppress metastasis of KL lung cancer.展开更多
基金Supported by the Korea Institute of Radiological and Medical Sciences Clinical Research Fund and Korea Science and Engineering Foundation
文摘AIM: To evaluate the prevalence and predictive factors of osteoporosis in patients with gastric adenocarcinoma alter gastrectomy.METHODS: The study included 133 patients diagnosed with gastric adenocarcinoma but who did not undergo prior diagnostic work-up for osteoporosis. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and vertebral deformity was assessed by plain X-rays. We evaluated the effects of age, sex, body mass index (BMI), anemia, back pain, vertebral deformity, tumor staging, reconstruction type, and past medical history to determine predictive factors of osteoporosis in these patients.RESULTS: The prevalence of osteoporosis in the lumbar spine was 38.3% (male, 28.9%; female, 54.0%), and 15.0% in the femoral neck (male, 10.8%; female, 22.0%). The vertebral deformity rate was 46.6% (male, 43.4%; female, 52.0%). Age, BMI and hemoglobin correlated with BMD (P 〈 0.01). In males, anemia and age 〉 64 years were independent predictive factors of osteoporosis in multivariate analysis. In females, back pain was an independent factor for osteoporosis.CONCLUSION: The results of this study revealed that prevalence of osteoporosis and vertebral bone deformity rate were high in gastric cancer patients, regardless of post-gastrectomy duration and operation type. Early diagnosis and a proper management plan must be established in these patients.
文摘BACKGROUND Extrahepatic metastasis(EHM)from hepatocellular carcinoma(HCC)occurs in 10%–15%of cases following initial treatment.The most frequent sites of EHM are the lung,lymph nodes,and bone.Gastrointestinal or brain metastasis from HCC is rarely reported.Here,we report a rare case of concurrent HCC metastases to the stomach,colon,and brain.CASE SUMMARY A 72-year-old male with a history of alcohol induced HCC presented with multiple intrahepatic recurrences and tumorous lesions in the stomach and ascending colon.Three years earlier,he underwent right hemihepatectomy,and 1 year ago,he had a video-assisted thoracoscopic wedge resection for pulmonary metastasis of HCC.We decided on surgical resection of the new metastases because of massive gastric bleeding and concern for possible colonic obstruction.The patient underwent gastric wedge resection and right hemicolectomy.Two weeks later,the patient developed dysarthria and mild cognitive disorder.Magnetic resonance imaging of the brain revealed a left frontal lobe lesion,and he underwent resection of a metastatic brain tumor.Unfortunately,he died 6 weeks after the last surgery due to hepatorenal syndrome.CONCLUSION Decision of surgery was carefully recommended in this case and may extend survival in other metastatic HCC patients with well-preserved hepatic function.
基金Korea Health Technology R&D Project through the Korea Health Industry Development Institute,Grant/Award Number:HI14C1324National Research Foundation of Korea,Grant/Award Numbers:2020R1A2C3007792,2019R1A2C3004155,2019H1A2A1075632+2 种基金NCI Lung Cancer SPORE,Grant/Award Number:P50CA70907Cancer Prevention and Research Institute of Texas(CPRIT),Grant/Award Number:RP160652“Team Science Award”of Yonsei University College of Medicine,Grant/Award Number:6-2021-0194。
文摘Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates EMT.Methods: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging system.Results: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner. Pharmacological inhibition of this axis via CAMKK2inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KLcancer cells in vivo.Conclusions: This study demonstrates that autophagy-derived acetyl-CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRASLKB1 co-mutated lung cancer cells and that inhibition of the autophagy/acetylCoA/acetyl-Snail axis using CAMKK2 or ACLY inhibitors could be a potentialtherapeutic strategy to suppress metastasis of KL lung cancer.