Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34<Superscript>+</Superscript> cells with granulocyte colony-stimulating factor and tumor necrosis factor-α

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the differentiation of CD34(+) cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34(+) cells during erythroid or megakaryocytic differentiation in the presence of TNF-alpha, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha would generate neutrophil progenitors and DCs together from human CD34(+) cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34(+) cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-alpha with G-CSF markedly decreased the number of CD15(+) cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c(+) cells were found to phagocytose CD15(+) cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c(+) cells generated by TNF-alpha and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c(+) cells induced by G-CSF plus TNF-alpha and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-alpha. These results indicate that the co-stimulation of human CD34(+) cells with G-CSF and TNF-alpha induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34(+) cells during erythroid differentiation.     

Neoadjuvant chemotherapy of irinotecan, 5-fluorouracil and leucovorin in patients with advanced rectal cancer. Report of two cases

We report on two patients with T3N1 rectal cancer treated with a combination of irinotecan, 5-fluorouracil and leucovorin as neoadjuvant chemotherapy. On days 1, 8 and 15 of this 4-week cycle, leucovorin (250 mg/m2) was administered in a 2-hour intravenous infusion, followed by 5-fluorouracil (500 mg/m2) in a 10-min intravenous bolus, and then irinotecan (80 mg/m2) in a 90-min intravenous infusion. During the chemotherapy, no grade 3-4 toxicities were observed. Two weeks after the completion of 2 cycles of this regimen, both patients underwent surgery without postoperative complications. The responses were one pathological and one macroscopic complete response. Both patients with T3 tumors were down-staged to pT0 and pT2, respectively. As for the N stage, both patients were down-staged to pN0. The combination of irinotecan/5-fluorouracil/leucovorin appears to be feasible and effective, and to have a potential as an optimal neoadjuvant therapy in patients with advanced rectal cancer.     

Protein-losing gastropathy associated with autoimmune disease: successful treatment with prednisolone

99m Tc-labeled human serum albumin scintigram showing abnormal radioactivity in the stomach. Endoscopic gastric biopsies revealed nonspecific inflammation, but marked intramural edema. Based on a slight elevation of antinuclear antibody level, autoimmune disease was suspected to be involved in this patient. Administration of prednisolone, as a diagnostic therapy, alleviated the hypoproteinemia, hypoalbuminemia, and hypercholesteremia. These findings suggest that an autoimmune mechanism could have been involved in this case of protein-losing gastropathy. Received: September 4, 2000 / Accepted: February 23, 2001     

Hinesol,a compound isolated from the essential oils of Atractylodes lancea rhizome,inhibits cell growth and induces apoptosis in human leukemia HL-60 cells

Hinesol is a unique sesquiterpenoid isolated from the Chinese traditional medicine, Atractylodes lancea rhizome. In a previous study, we screened various natural products in human leukemia HL-60 cells and identified an essential oil fraction from A. lancea rhizome that exhibited apoptosis-inducing activity in these cells; hinesol was subsequently shown to be the compound responsible for this apoptosis-inducing activity. In this study, we describe the cytotoxic effects and molecular mechanisms of hinesol in HL-60 cells. The antitumor effect of hinesol was associated with apoptosis. When HL-60 cells were treated with hinesol, characteristic features of apoptosis, such as nuclear fragmentation and DNA fragmentation, were observed. These growth-inhibitory and apoptosis-inducing activities of hinesol in leukemia cells were much stronger than those of β-eudesmol, another compound isolated from the essential oil fraction. Furthermore, hinesol induced activation of c-Jun N-terminal kinase (JNK), but not p38, prior to the onset of apoptosis. These results suggested that hinesol induced apoptosis through the JNK signaling pathway in HL-60 cells. Therefore, hinesol may represent a novel medicinal drug having indications in the treatment of various cancers, including leukemia.

     

Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 ¹¹C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) ¹¹C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on ¹¹C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 ¹¹C-choline-PET/CT scans, respectively. In 27 cases (48.2%), ¹¹C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ± 3.21, 5.95 ± 3.96, 6.73 ± 5.04, and 7.91 ± 3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.     

Comparison of laparoscopic Toupet and laparoscopic Nissen fundoplications in neurologically normal children

Introduction

We compared laparoscopic Toupet fundoplication (LTF) and laparoscopic Nissen fundoplication (LNF) in neurologically normal children.

Methods

Forty neurologically normal children who were followed up for more than 3 years after LTF (n = 22) or LNF (n = 18) were reviewed retrospectively. LTF and LNF were performed between 2006 and 2012.

Results

There were no significant differences in gender (LTF, 15 male and 7 female patients; LNF:, 12 male and 6 female patients), mean age at surgery (LTF vs LNF: 2.5 vs 2.3 years), mean weight at surgery (LTF vs LNF: 9.6 vs 8.9 kg), preoperative symptoms, preoperative pH monitoring (pH <4) (LTF vs LNF: 26.7% vs 21.8%), mean operative time (LTF vs LNF: 117 vs 126 min), postoperative recommencement of enteral feeding (LTF vs LNF: 3.7 vs 3.8 days), or duration of hospitalization (LTF vs LNF: 5.5 vs 6.3 days). Intraoperative complications were esophageal trauma (LTF; n = 1; 4.5%) and liver trauma (LNF; n = 1; 5.6%) (P = 0.70). Post‐LTF complications were wrap stenosis (n = 1; 4.5%), and post‐LNF complications were wrap stenosis (n = 1; 5.5%) and gastric outlet obstruction (n = 1; 5.5%) (P = 0.43); all were managed conservatively. No case required conversion to open repair. There was no recurrence after LTF, but there were three cases (16.7%) after LNF (P = 0.08). Reoperation was performed at 4, 11, and 13 months, respectively.

Conclusion

Despite LTF and LNF appearing to be equally effective, three LNF cases required reoperation.     

Potential Usefulness of Early Potassium Supplementation for Preventing Severe Hypokalemia Induced by Liposomal Amphotericin B in Hematologic Patients: A Retrospective Study

Purpose

Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB–induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients.

Therapeutic Dilemma of Sarcoidosis and Treatment-naïve Hepatitis C Manifesting as Tattoo Reactions

A 23-year-old man had an 8-day history of fatigue and dry cough and papulo-nodular reactions on his extensive tattoos. Chest radiography revealed several small granular shadows, and a transbronchial lung biopsy showed non-caseating epithelioid cell granuloma. A skin biopsy of the tattooed area showed histiocytic infiltrates with phagocytized tattoo pigment. Antibody tests for hepatitis C virus were positive. The patient was successfully treated with corticosteroid therapy, and after inflammation was suppressed, he received delayed anti-viral therapy. Sarcoidosis should be considered as a concurrent condition if papules are presented on the tattoos of patients with hepatitis C.