OBJECTIVES: The purpose of this study is to identify whether the change of pH affects the proliferation and the differentiation of human bone marrow stem cells (hBMSCs) and what mechanism is underlied. METHODS: To achieve objective of this study, hBMSCs were cultivated in the conditioned media adjusted to potential of hydrogen (pH) ranging from 6.4 to 8.0 using addition of hydrochloric acid (HCl) and sodium hydroxide (NaOH). The ratio of proliferation of hBMSCs according to the change of pH was measured for 24 h, 48 h, and 72 h using water-soluble tetrazolium salt (WST)-8 method. To elucidate the mechanism involved, hBMSCs was subjected to blocking extracellular signal-regulated kinases (ERK) and calcium sensing receptor (CaSR) activation. The Osteogenic-related genes and alkaline phosphatase (ALP) activity were tested under the conditioned media. RESULTS: The proliferation of hBMSCs was promoted under extracellular alkali conditions (pH 7.6~8.0) via CaSR/ERK pathway. On the other hand, the differentiation was inhibited/delayed via decreased ALP activity besides gene expression at pH 8.0. CONCLUSION: Extracellular alkali or acidic surrounding according to pH alteration can play a crucial role in hBMSC behavior including the proliferation and the differentiation.
Alkalies ; Alkaline Phosphatase ; Bone Marrow ; Bone Marrow Cells ; Cell Differentiation ; Cell Proliferation ; Culture Media, Conditioned ; Extracellular Signal-Regulated MAP Kinases ; Gene Expression ; Hand ; Humans ; Hydrochloric Acid ; Hydrogen ; Hydrogen-Ion Concentration ; Hydroxides ; Receptors, Calcium-Sensing ; Sodium Hydroxide ; Stem Cells

OBJECTIVES: The purpose of this study is to identify whether the change of pH affects the proliferation and the differentiation of human bone marrow stem cells (hBMSCs) and what mechanism is underlied. METHODS: To achieve objective of this study, hBMSCs were cultivated in the conditioned media adjusted to potential of hydrogen (pH) ranging from 6.4 to 8.0 using addition of hydrochloric acid (HCl) and sodium hydroxide (NaOH). The ratio of proliferation of hBMSCs according to the change of pH was measured for 24 h, 48 h, and 72 h using water-soluble tetrazolium salt (WST)-8 method. To elucidate the mechanism involved, hBMSCs was subjected to blocking extracellular signal-regulated kinases (ERK) and calcium sensing receptor (CaSR) activation. The Osteogenic-related genes and alkaline phosphatase (ALP) activity were tested under the conditioned media. RESULTS: The proliferation of hBMSCs was promoted under extracellular alkali conditions (pH 7.6~8.0) via CaSR/ERK pathway. On the other hand, the differentiation was inhibited/delayed via decreased ALP activity besides gene expression at pH 8.0. CONCLUSION: Extracellular alkali or acidic surrounding according to pH alteration can play a crucial role in hBMSC behavior including the proliferation and the differentiation.
Alkalies ; Alkaline Phosphatase ; Bone Marrow ; Bone Marrow Cells ; Cell Differentiation ; Cell Proliferation ; Culture Media, Conditioned ; Extracellular Signal-Regulated MAP Kinases ; Gene Expression ; Hand ; Humans ; Hydrochloric Acid ; Hydrogen ; Hydrogen-Ion Concentration ; Hydroxides ; Receptors, Calcium-Sensing ; Sodium Hydroxide ; Stem Cells

PURPOSE: To analyze retrospectively the outcome of postoperative radiation therapy with or without concurrent chemotherapy for curatively resected stage II pancreatic cancer with T3 or N1 disease. MATERIALS AND METHODS: Between January 1996 and December 2005, twenty-eight patients completed adjuvant radiation therapy at Ajou University Hospital. The patients had either pathologic T3 stage or N1 stage. The radiation target volume encompassed the initial tumor bed identified preoperatively, resection margin area and celiac nodal area. In the case of N1 patients, the radiation field extended to the lower margin of the L3 vertebra for covering both para-aortic lymph nodes bearing area. The median total radiation dose was 50 Gy. Ten patients received concurrent chemotherapy. RESULTS: Thirteen patients (46%) showed loco-regional recurrences. The celiac axis nodal area was the most frequent site (4 patients). Five patients showed both loco-regional recurrence and a distant metastasis. Patients with positive lymph nodes had a relatively high probability of a distant metastasis (57.1%). Patients that had a positive resection margin showed a relatively high local failure rate (57.1%). The median disease-free survival period of all patients was 6 months and the 1- and 2-year disease free survival rates were 27.4% and 8.2%, respectively. The median overall survival period was 9 months. The 2- and 3-year overall survival rates were 31.6% and 15.8%, respectively. CONCLUSION: The pancreatic cancer patients with stage II had a high risk of local failure and a high risk of a distant metastasis. We suggest the concurrent use of an effective radiation-sensitizing chemotherapeutic drug and adjuvant chemotherapy after postoperative radiation therapy for the treatment of patients with stage II pancreatic cancer.
Axis, Cervical Vertebra ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Pancreatic Neoplasms* ; Recurrence ; Retrospective Studies ; Spine ; Survival Rate