Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 “functional” binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-1 expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules

Time-Course of Salivary Metabolomic Profiles during Radiation Therapy for Head and Neck Cancer

Oral mucositis (OM) is one of the most frequently observed adverse oral events in radiation therapy for patients with head and neck cancer. Thus, objective evaluation of OM severity is needed for early and timely intervention. Here, we analyzed the time-course of salivary metabolomic profiles during the radiation therapy. The severity of OM (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0) of nine patients with head and neck cancer was evaluated. Partial least squares regression-discriminant analysis, using samples collected before radiation therapy, showed that histidine and tyrosine highly discriminated high-grade OM from low-grade OM before the start of radiation therapy (significant difference, p = 0.048 for both metabolites). Further, the pretreatment concentrations of gamma-aminobutyric acid and 2-aminobutyric acids were higher in the high-grade OM group. Although further validations are still necessary, this study showed potentially associated metabolites with worse radiotherapy-related OM among patients with head and neck cancer

A Case of Total Proctocolectomy by Reduced Port Surgery for Refractory Ulcerative Colitis

We report the case of a 40-year-old woman with refractory ulcerative colitis (UC) whose condition did not improve despite aggressive medical therapy with a corticosteroid and an immunosuppressor. The patient underwent a total proctocolectomy by reduced port surgery (RPS). A vertical incision of 30mm was made through the umbilicus, and a laparoscope port and two working or assistant laparoscopic ports were inserted through the fascia. A 5mm port was used as the terminal ileostomy site and another 5mm port was used as a drain site (marked preoperatively). The operator used a standard laparoscopic 5mm atraumatic grasper for the left hand and a standard laparoscopic dissector or an Enseal energy device for the right hand. An ileal J-pouch was created extra-corporeally from the terminal ileum and then an ileal pouch–anal anastomosis (IPAA) was created by hand suturing. The diverting loop ileostomy was brought out through the right iliac fossa, and there was 30cm of ileum between the diverting loop ileostomy and the IPAA. The surgical procedures were very similar to those normally used in laparoscopic colectomy. The duration of the surgery was 465min, and blood loss was estimated at 240ml. No intraoperative complications occurred, and conversion to conventional laparoscopic or open surgery was not needed. Laparoscopic total proctocolectomy using RPS (compared with standard laparoscopic surgery) may be preferred for young women because it reduces the wound size, minimizes postoperative pain, and enhances cosmesis

Metabolomic profiling reveals salivary hypotaurine as a potential early detection marker for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage ≥1 advanced MRONJ (n = 9) with that of controls without MRONJ before chemotherapy (n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage ≥1 advanced MRONJ (n = 8) and controls without MRONJ after chemotherapy (n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ