Metachronous primary cancer of the tongue and malignant lymphoma of the small intestine: A case report.

RATIONALE: Oral cancer often causes secondary primary cancers in the upper gastrointestinal tract. However, there are no reports of secondary primary cancers in patients with oral squamous cell carcinoma and malignant lymphoma of the small intestine. This report describes a case of metachronous multiple primary cancers of the tongue and small intestine malignant lymphoma. PATIENTS CONCERNS: The patient was admitted to our department with the chief complaint of pain in the right tongue. Partial tongue resection and supraomohyoid neck dissection were performed. One year after surgery, the patient experienced abdominal pain and bloody stools. DIAGNOSIS: Diffuse large B-cell lymphoma (DLBCL) was diagnosed via histological examination. INTERVENTIONS: A terminal ileum resection was performed. Postoperatively, the patient received 6 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP). OUTCOMES: Five years after his initial diagnosis, there is no evidence of recurrence, metastasis, or other primary cancer. LESSONS: Oral cancer patients should always be followed up owing to a possibility of malignant tumors in other areas.

Secreted Factors from Stem Cells of Human Exfoliated Deciduous Teeth Directly Activate Endothelial Cells to Promote All Processes of Angiogenesis.

Diabetes is a major risk factor for atherosclerosis and ischemic vascular diseases. Recently, regenerative medicine is expected to be a novel therapy for ischemic diseases. Our previous studies have reported that transplantation of stem cells promoted therapeutic angiogenesis for diabetic neuropathy and ischemic vascular disease in a paracrine manner, but the precise mechanism is unclear. Therefore, we examined whether secreted factors from stem cells had direct beneficial effects on endothelial cells to promote angiogenesis. The soluble factors were collected as conditioned medium (CM) 48 h after culturing stem cells from human exfoliated deciduous teeth (SHED) in serum-free DMEM. SHED-CM significantly increased cell viability of human umbilical vein endothelial cells (HUVECs) in MTT assays and accelerated HUVECs migration in wound healing and Boyden chamber assays. In a Matrigel plug assay of mice, the migrated number of primary endothelial cells was markedly increased in the plug containing SHED-CM or SHED suspension. SHED-CM induced complex tubular structures of HUVECs in a tube formation assay. Furthermore, SHED-CM significantly increased neovascularization from the primary rat aorta, indicating that SHED-CM stimulated primary endothelial cells to promote comprehensive angiogenesis processes. The angiogenic effects of SHED-CM were the same or greater than the effective concentration of VEGF. In conclusion, SHED-CM directly stimulates vascular endothelial cells to promote angiogenesis and is promising for future clinical application.

Secreted factors from cultured dental pulp stem cells promoted neurite outgrowth of dorsal root ganglion neurons and ameliorated neural functions in streptozotocin-induced diabetic mice.

AIMS/INTRODUCTION: Transplantation of stem cells promotes axonal regeneration and angiogenesis in a paracrine manner. In the present study, we examined whether the secreted factors in conditioned medium of stem cells from human exfoliated deciduous teeth (SHED-CM) had beneficial effects on diabetic polyneuropathy in mice. MATERIALS AND METHODS: Conditioned medium of stem cells from human exfoliated deciduous teeth was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM), and separated into four fractions according to molecular weight. Dorsal root ganglion neurons from C57BL/6J mice were cultured with SHED-CM or DMEM to evaluate the effect on neurite outgrowth. Streptozotocin-induced diabetic mice were injected with 100 µL of SHED-CM or DMEM into the unilateral hindlimb muscles twice a week over a period of 4 weeks. Peripheral nerve functions were evaluated by the plantar test, and motor and sensory nerve conduction velocities. Intraepidermal nerve fiber densities, capillary number-to-muscle fiber ratio, capillary blood flow and morphometry of sural nerves were also evaluated. RESULTS: Conditioned medium of stem cells from human exfoliated deciduous teeth significantly promoted neurite outgrowth of dorsal root ganglion neurons compared with DMEM. Among four fractions of SHED-CM, the only fraction of <6 kDa promoted the neurite outgrowth of dorsal root ganglion neurons. In addition, SHED-CM significantly prevented decline in sensory nerve conduction velocities compared with DMEM in diabetic mice. Although SHED-CM did not improve intraepidermal nerve fiber densities or morphometry of sural nerves, SHED-CM ameliorated the capillary number-to-muscle fiber ratio and capillary blood flow. CONCLUSIONS: These results suggested that SHED-CM might have a therapeutic effect on diabetic polyneuropathy through promoting neurite outgrowth, and the increase in capillaries might contribute to the improvement of neural function.

Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic ß-cell function.

OBJECTIVE: Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic ß-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic ß-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on ß-cell function and survival. RESEARCH DESIGN AND METHODS: Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic ß-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. RESULTS: Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and ß-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic ß-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on ß-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. CONCLUSIONS: These findings suggest that SHED-CM provides direct protection and encourages the propagation of ß-cells, and has potential as a novel strategy for treatment of diabetes.

Diabetic foot wounds in haemodialysis patients: 2-year outcome after percutaneous transluminal angioplasty and minor amputation.

Critical limb ischaemia (CLI) is known to be associated with high mortality. In some patients, surgery cannot be performed due to high risk of perioperative death and complications. In other cases, there is only pain at rest but no wound. Therefore, it is difficult to accurately predict the prognosis of individual patients. We examined the prognosis of CLI cases in which therapeutic footwear was made for ambulation after wounds healed. The subjects were 31 haemodialysis patients with diabetic foot wounds, which were treated with percutaneous transluminal angioplasty and minor amputation. The subjects were 22 men and 9 women. Female patients were significantly older than male patients (P = 0.046). Two-year postoperative outcomes were survival in 19 patients and death in 12 patients. Eight of twelve deceased patients had a history of coronary intervention. There were 8 deaths among 13 patients with such history, indicating a marginally significant increase in the mortality rate (P = 0.060). Re-amputation was performed in 6 of 19 patients who survived. Two years postoperatively, 41.9% of patients overall survived without re-amputation. It is important to increase the number of cases for further study to improve the well-being of CLI patients and to examine medical economics.

[Acute myocardial infarction with variable clinical manifestations: probable catastrophic primary antiphospholipid antibody syndrome: a case report].

A 62-year-old diabetic man was admitted to our hospital because of acute myocardial infarction. Emergent coronary angiography showed multiple thromboembolic occlusions in the distal circumflex and anterior descending arteries. For the first 2 weeks of hospitalization, he suffered multiple organ manifestations including the gastrointestinal, central nervous, renal and respiratory systems. The anticardiolipin beta2GP1 complex antibody titer on the 15th day was as high as 27.2 U/l (normal value < 3.5). These clinical manifestations and laboratory findings suggested catastrophic antiphospholipid antibody syndrome. He was discharged on the 83rd day with anticoagulant therapy and regular hemodialysis. Acute myocardial infarction is rare as the initial manifestation of catastrophic antiphospholipid antibody syndrome.

[Right coronary air embolism secondary to bowel infarction: a case report].

An 81-year-old man with broad cerebral infarction presented with coronary air embolism secondary to bowel infarction and developed cardiogenic shock. Electrocardiography revealed ST elevation in the inferior leads and complete atrioventricular block with atrial fibrillation. Emergent angiography showed total occlusion of the right coronary artery without apparent thrombi. A multifunctional probe catheter was inserted into the right coronary artery for selective angiography. A moderate amount of air was aspirated from the catheter. The diagnosis was coronary air embolism. Coronary flow was restored after aspiration and normal saline flushing. Computed tomography showed massive portal venous gas. Emergent laparotomy disclosed broad bowel necrosis. The coronary air emboli may have originated from the portal vein and passed through the intrahepatic (portal to hepatic) shunt and patent foramen ovale(paradoxical embolization).

Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation.

OBJECTIVES: We examined whether oral folate supplementation would rescue a hypercholesterolemia (HC)-related impairment of ischemia-induced angiogenesis. BACKGROUND: Folate protects against endothelial dysfunction, but the effect of folate supplementation on angiogenesis is little known. METHODS: Sprague-Dawley rats were divided into four groups. Control rats were fed a normal diet (n = 18); HC rats (n = 18) were fed 2% cholesterol diet; and HC + folate (HC+F) rats were fed an HC diet with oral folate (0.003% in water). The left femoral artery and vein were surgically excised, and angiogenesis in the ischemic limb was evaluated. We also examined the effects of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on angiogenesis in the HC+F state. RESULTS: Laser Doppler blood flow (LDBF) analysis showed lower ischemic/normal LDBF ratio in the HC group than in the control group. Angiographic and histologic analyses on day 14 revealed a smaller angiographic score (p < 0.001) and capillary density (p < 0.001) in the HC group than in controls, which were associated with reduced tissue NOx and cyclic guanosine monophosphate (cGMP) levels. The LDBF ratio, angiographic score, and capillary density were significantly restored in the HC+F group (p < 0.01 vs. HC), which were associated with increased serum folate and tissue NOx and cGMP levels. Finally, L-NAME treatment abolished the beneficial action of folate on angiogenesis in the HC state. CONCLUSIONS: Ischemia-induced angiogenesis was inhibited by HC, which was rescued by oral folate supplementation, at least in part, via an NO-dependent manner.

Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization.

A subset of human peripheral blood mononuclear cells (PB-MNCs) differentiate into endothelial progenitor cells (EPCs) that participate in postnatal neovascularization. Although tissue ischemia can mobilize EPCs from bone marrow, the effects of hypoxia on differentiation and angiogenic function of EPCs are little known. We examined whether hypoxic conditioning would modulate differentiation and function of human PB-MNC-derived EPCs. A subset of PB-MNCs gave rise to EPC-like attaching (AT) cells under either normoxic or hypoxic conditions. However, hypoxia much enhanced the differentiation of AT cells from PB-MNCs compared with normoxia. AT cells released vascular endothelial growth factor (VEGF) protein and expressed CD31 and kinase insert domain receptor/VEGFR-2, endothelial lineage markers, on their surface, which were also enhanced by hypoxia. Both a neutralizing anti-VEGF mAb and a KDR-specific receptor tyrosine kinase inhibitor, SU1498, suppressed PB-MNC differentiation into EPC-like AT cells in a dose-dependent manner. Migration of AT cells in response to VEGF as examined by a modified Boyden chamber apparatus was also enhanced by hypoxia. Finally, in vivo neovascularization efficacy was significantly enhanced by in vitro hypoxic conditioning of AT cells when cells were transplanted into the ischemic hindlimb of immunodeficient nude rats. In conclusion, hypoxia directly stimulated differentiation of EPC-like AT cells from human PB-MNC culture. Moreover, hypoxic preconditioning of AT cells before in vivo transplantation is a useful means to enhance therapeutic vasculogenesis.