Peripheral blood stem cell transplantation ; an update

Patients with a number of different malignancies have been treated with high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT). PBSC already replaced bone marrow as the source of autologous hematopoietic progenitor support. This is due to ease of collection, rapid engraftment and less possibility of tumor cell contamination in the graft. Furthermore, allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF) mobilized PBSC is now being increasingly performed. Recent advance of clinical PBSCT and new strategies are stressed in this review. New strategies include CD 34+cell purification, ex vivo expansion of PBSC and PBSC as a target cell for gene therapy. Major future advance may occur better understanding of the mechanism of mobilization and the biology of PBSC

Investigation of Effective Modification Treatments for Titanium Membranes

Titanium membranes are used for guided bone regeneration in implant therapy. However, as a bioinert material, titanium does not have the ability to accelerate bone formation. Various titanium surface treatments to confer bioactivity have been demonstrated; however, there are concerns about the influence of chemical treatments for thin titanium membranes. This study investigated the influence of surface modifications on the structure of titanium membranes. Titanium membranes of 20 μm thickness were treated with acid or alkali solutions, and we evaluated their surface structure, wettability, thickness, and mechanical strength compared to non-treated membranes. Alkali-treated titanium membranes displayed the formation of nanoscale pore structures on their surfaces, enhanced hydrophilicity, and almost same thickness compared with acid-treated membranes. Furthermore, the tensile strength of alkali-treated membranes was comparable to non-treated membranes. These results suggest that alkali treatment is an appropriate surface modification method for titanium membranes

Homeostatic Mass Control in Gastric Non-Neoplastic Epithelia under Infection of Helicobacter pylori: An Immunohistochemical Analysis of Cell Growth, Stem Cells and Programmed Cell Death

We evaluated homeostatic mass control in non-neoplastic gastric epithelia under Helicobacter pylori (HP) infection in the macroscopically normal-appearing mucosa resected from the stomach with gastric cancer, immunohistochemically analyzing the proliferation, kinetics of stem cells and programmed cell death occurring in them. Ki67 antigen-positive proliferating cells were found dominantly in the elongated neck portion, sparsely in the fundic areas and sporadically in the stroma with chronic infiltrates. CD117 could monitor the kinetics of gastric stem cells and showed its expression in two stages of gastric epithelial differentiation, namely, in transient cells from the gastric epithelial stem cells to the foveolar and glandular cells in the neck portion and in what are apparently progenitor cells from the gastric stem cells in the stroma among the infiltrates. Most of the nuclei were positive for ssDNA in the almost normal mucosa, suggesting DNA damage. Cleaved caspase-3-positive foveolar cells were noted under the surface, suggesting the suppression of apoptosis in the surface foveolar cells. Besides such apoptosis of the foveolar cells, in the severely inflamed mucosa apoptotic cells were found in the neck portion where most of the cells were Ki67 antigen-positive proliferating cells. Beclin-1 was recognized in the cytoplasm and in a few nuclei of the fundic glandular cells, suggesting their autophagic cell death and mutated beclin-1 in the nuclei. Taken together, the direct and indirect effects of HP infection on the gastric epithelial proliferation, differentiation and programmed cell death suggested the in-situ occurrence of gastric cancer under HP infection

A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population

Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55–8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42–8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14–3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population

Cancer genome profiling for GI cancers

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine’s current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n = 30), colorectal (n = 25), biliary tract (n = 15), gastric (n = 11), and hepatocellular carcinoma (n = 8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n = 1), colorectal (n = 3), and small bowel cancers (n = 1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n = 40) and the inability to participate in clinical trials (n = 10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs

Current status of hematopoietic stem cell transplantation and umbilical cord blood bank in Chugoku-Shikoku area

The hematopoietic stem cell transplantation (HSCT) is rapidly and widely spreading in the treatment strategy of various types of cancers, since peripheral and umbilical cord blood (CB) have been introduced as new sources of transplantable cells in addition to ordinary bone marrow cells. In this report, the current status of HSCT was reviewed. CB is rich in hematopoietic stem/progenitor cells, which have high proliferative potential. T cells in CB are speculated to be immature and immune-tolerable cells with less potential to cause acute or chronic graft versus host disease (GVHD), which are directly related with transplant-related morbidity and mortality. Furthermore, transplants with CB are not strictly restricted by a HLA-disparity. On the other hand, the less number of collected cells from CB is a major problem when the cells are applied for clinical transplantation, because the lower number of infused cells often result in engraftment failure. Further, we have no data of the viability after long term cryopreservation. We must carefully judge the usefulness of CB as a cell source for transplantation, but the benefits of CB may have a possibility to overcome these disadvantage in the near future. Finally, the activity of cord blood bank in Chugoku-Shikoku area, which was started from August 1998, was also introduced

Benzene Metabolite 1,2,4-Benzenetriol Induces Halogenated DNA and Tyrosines Representing Halogenative Stress in the HL-60 Human Myeloid Cell Line

Background: Although benzene is known to be myelotoxic and to cause myeloid leukemia in humans, the mechanism has not been elucidated

Total parenteral nutrition on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation

The resting energy expenditure (REE) and the respiratory quotient (RQ) were measured longitudinally using indirect calorimetry to examine the effects of total parenteral nutrition (TPN) on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation (PBSCT). There were six children (two males and four females) and the age ranged from five to 13 years (median, eight yrs.). The diagnosis included acute lymphocytic leukemia (ALL ; 4), neuroblastoma (NBL ; 1) and primitive neuroectodermal tumor (PNET ; 1). TPN was started after the patients were stabilized following PBSCT (group A ; n=3) or before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B ; n=3). Duration of HCC before PBSCT was identical between the two groups (six to eight days). Average total calorie and protein intake during HCC was significantly higher for group B than for group A. The %REE, the percentage of REE to the predicted basal energy expenditure (BEE), in group A showed 133±19%, 129±14% and 146±11% during three periods of HCC (days -8 to -1 of PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to 20% lower than those in group A at all periods. Carbohydrate oxidation rates during HCC in group A were significantly lower than those in group B, and those were not different between both groups during post-PBSCT periods. Fat oxidation rates in both groups were similar at all stages of periods. In contrast, protein degradation rates in group A were significantly higher than those in group B at all stages of the period. From these results, we concluded that commencement of TPN administration prior to HCC in the patients undergoing PBSCT provides beneficial effects to maintain better energy metabolic and nutritional status

Factors related to renal cortical atrophy development after glucocorticoid therapy in IgG4-related kidney disease: a retrospective multicenter study.

Background: In immunoglobulin G4-related kidney disease (IgG4-RKD), focal or diffuse renal cortical atrophy is often observed in the clinical course after glucocorticoid therapy. This study aimed to clarify the factors related to renal atrophy after glucocorticoid therapy in IgG4-RKD. Methods: We retrospectively evaluated clinical features including laboratory data and computed tomography (CT) findings before and after glucocorticoid therapy in 23 patients diagnosed with IgG4-RKD, all of whom were followed up for more than 24 months. Results: Seventeen patients were men, and six were women (average age 62.0 years). Average follow-up period was 54.9 months. The average estimated glomerular filtration rate (eGFR) at diagnosis was 81.7 mL/min/1.73 m2. All patients had had multiple low-density lesions on contrast-enhanced CT before glucocorticoid therapy, and showed disappearance or reduction of these lesions after it. Pre-treatment eGFR and serum IgE level in 11 patients in whom renal cortical atrophy developed 24 months after the start of glucocorticoid therapy were significantly different from those in 12 patients in whom no obvious atrophy was found at that time (68.9 ± 30.1 vs 93.5 ± 14.1 mL/min/1.73 m2, P = 0.036, and 587 ± 254 vs 284 ± 263 IU/mL, P = 0.008, respectively). Pre-treatment eGFR and serum IgE level were also significant risk factors for renal atrophy development 24 months after the start of therapy with an odds ratio of 0.520 (per 10 mL/min/1.73 m2, 95% confidence interval (CI) 0.273-0.993, P = 0.048) and 1.090 (per 10 IU/mL, 95% CI: 1.013-1.174, P = 0.022), respectively, in age-adjusted, sex-adjusted, serum IgG4 level-adjusted logistic regression analysis. Receiver operating characteristic curve analysis showed that eGFR of less than 71.0 mL/min/1.73 m2 and serum IgE of more than 436.5 IU/mL were the most appropriate cutoffs and yielded sensitivity of 63.6% and specificity of 100%, and sensitivity of 90.9% and specificity of 75.0%, respectively, in predicting renal atrophy development. Conclusions: This study suggests that pre-treatment renal insufficiency and serum IgE elevation predict renal atrophy development after glucocorticoid therapy in IgG4-RKD. © 2016 The Author(s)