The mechanism underlying extracellular adenosine-induced caspase-independent apoptosis in HuH-7 human hepatoma cells is not fully understood. The present study investigated the role for apoptosis-inducing factor (AIF)-homologous mitochondrion-associated inducer of death (AMID) in the pathway.To see the implication of AMID in adenosine-induced HuH-7 cell apoptosis, real-time reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescent cytochemistry, time-laps GFP monitoring, cell cycle analysis, flow cytometry, Western blotting, cell viability assay, and TUNEL staining were carried out.Adenosine upregulated AMID expression in HuH-7 cells, and translocated AMID from the cytosol into the nucleus. Adenosine induced HuH-7 cell apoptosis, and the effect was further enhanced by overexpressing AMID. Adenosine-induced HuH-7 cell apoptosis, alternatively, was inhibited by knocking-down AMID.The results of the present study provide evidence for AMID as a critical factor for adenosine-induced caspase-independent HuH-7 cell apoptosis.
Abstract: Specific types of early gastric cancer were investigated in accordance with the cancer surface area and the degree of penetration by means of quantitative measurements of the surface area of early gastric cancer using the interactive image analysis system. The results indicated a significant correlation between the surface area and the penetration depth in ordinary early gastric cancer. However these correlations were not observed in both well and poorly differentiated adenocarcinoma cases of the so‐called PEN and SUPER types, which showed a significant specificity when compared with ordinary early gastric cancer. The PEN and SUPER types of early gastric cancer also exhibited various clinicopathological characteristics, and it was suggested that the poorly differentiated PEN type might be the initial lesion of a linitis plastica type gastric cancer. Examination of the conditions of the mucosa surrounding the cancer revealed a difference between the PEN and the SUPER types, and this suggested that the environment at the site of a cancer growth influences the type of growth and the spread of early gastric cancer.
Adenoviral vectors, both oncolytic viruses and gene delivery vectors, are among the earliest approved and commercialised vectors for gene therapy. Adenoviruses have high cytotoxicity and immunogenicity. Therefore, lentiviruses or adeno-associated viruses as viral vectors and herpes simplex virus as an oncolytic virus have recently drawn attention. Thus, adenoviral vectors are often considered relatively obsolete. However, their high cargo limit and transduction efficiency are significant advantages over newer viral vectors. This review provides an overview of the new-generation adenoviral vectors. In addition, we describe the modification of the fiber knob region that enhances affinity of adenoviral vectors for cancer cells and the utilisation of cancer-cell-specific promoters to suppress expression of unwanted transgenes in non-malignant tissues.
The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1) expression in human keratinocyte was investigated. ICAM-1 is known to mediate skin inflammation. Among the flavonoids tested, taxifolin was the most potent in inhibiting interferon gamma (IFN gamma)-induced ICAM-1 protein as well as mRNA expression in human keratinocytes. Much smaller dosages of taxifolin were required in primary keratinocytes compared to HaCaT (immortalized cell) to achieve similar levels of inhibition in the inducible ICAM-1 expression. Regulation of inducible ICAM-1 expression by taxifolin was at transcriptional level by inhibiting the activation of signal transducers and activators of transcription (STAT)1 and protein tyrosine phosphorylation of Janus kinase (JAK)1 suggesting that the JAK-STAT pathway may be the molecular site of action of taxifolin. Finally, taxifolin pre-treatment also potently inhibited IFN gamma-induced ICAM-1 expression in a reconstructed human skin equivalent suggesting therapeutic potential of taxifolin in skin pathological conditions related to increased cell adhesion and inflammation.
We report a case of bilateral renal cell carcinoma which developed during about 14 years of hemodialysis. The patient of male was a 39-year-old with a chief complaint of macrohematuria 14 years prior to dialysis therapy. Computed tomography revealed multiple cystic changes of bilateral kidneys and a high density area in the right kidney. He was admitted to our department in April 1988. He was suspected of renal cell carcinoma of the right kidney and underwent transperitoneal radical nephrectomy on the right kidney. The left kidney was also resected simultaneously in part because it failed to function and in part because the long-term hemodialyzed patients are considered to have a complication of renal cell carcinoma at a high frequency. Pathological diagnosis was bilateral acquired cystic disease of the kidney (ACDK) with renal cell carcinoma. The kidney develops multiple cystic changes following long-term hemodialysis, which forms a high risk for development of renal cell carcinoma. This is a case of bilateral renal cell carcinoma which occurred after long-term hemodialysis, was reported with discussion and reference to the literature.
We evaluated calcium metabolism and bone demineralization by measuring specific markers for bone reabsorption and bone mineral density in patients with an intestinal neobladder.We studied 33 men 55 to 72 years old who underwent creation of an orthotopic sigmoid (23), ileocolic (8) or ascending colon (2) neobladder after cystectomy. Mean followup plus or minus standard deviation (SD) was 28.4+/-30.1 months (range 4 to 114). Serum electrolytes and arterial blood gases were measured. As markers of bone absorption we assayed urinary pyridinoline, deoxypyridinoline and N-terminal pyridinoline cross-linked telopeptides, and serum pyridinoline cross-linked C-terminal telopeptide of type I collagen. Bone mineral density of the spine and femur was determined by dual x-ray absorptiometry.Mean blood pH plus or minus SD was 7.38+/-0.04 (range 7.29 to 7.43). Mean plasma bicarbonate was 22.9+/-3.4 mmol./l. and mean base excess was -1.63+/-3.61 mmol./l. Serum sodium, potassium, calcium, alkaline phosphatase and phosphate were normal in most patients. Mean serum chloride was 108.0+/-3.5 mEq./l., and was elevated in 9 of the 33 patients (27.3%). Serum intact parathyroid hormone was normal in all patients, osteocalcin was increased in 2 and 1alpha, 25-dihydroxyvitamin D3 was decreased in 2. Pyridinoline cross-linked C-terminal telopeptide of type I collagen was higher in 19 of 33 cases (57.6%) and N-terminal pyridinoline cross-linked telopeptides were elevated in 6 (18.2%). Pyridinoline and deoxypyridinoline were higher than normal in 19 (57.6%) and 7 (21.2%) patients, respectively. C-terminal telopeptide of type I collagen and deoxypyridinoline significantly correlated with serum pH (p = 0.017 and 0.0418, respectively). Z score for the bone mineral density of L2 to L4, the femoral neck and Ward's triangle was -0.350+/-1.031, -0.82+/-0.99 and -0.94+/-1.01, respectively.In patients with a neobladder of intestinal segments metabolic acidosis results in increased bone absorption and decreased bone mass. Thus, attention should be given to bone metabolism in patients with even mild acidosis after orthotopic neobladder creation.
Naftopidil, an α1-adrenoceptor blocker, has been clinically used for the treatment of benign prostate hyperplasia and hypertension. Emerging evidence has shown that naftopidil exhibits an antitumor effect on a variety of cancer types including prostate cancer. The aim of the present study was to investigate naftopidil-induced apoptosis in human malignant mesothelioma cells and to shed light on the underlying mechanism.3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, western blotting, and enzymatic assay of caspase-3, -8, and -9 activities were carried out on human malignant mesothelioma cell lines NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells. To knock-down α1D-adrenoceptor, siRNA to silence human α1D-adrenoceptor-targeted gene was constructed and transfected into cells.Naftopidil induced apoptosis in all the investigated malignant mesothelioma cells, and a similar effect was obtained with prazosin, another α1-adrenoceptor blocker. α1-Adrenoceptor is linked to Gq/11 protein involving activation of protein kinase C (PKC). Naftopidil-induced reduction in cell viability was inhibited by GF109203X, while prazosin-induced in cell viability was less affected. Knocking-down α1D-adrenoceptor promoted malignant mesothelioma cell proliferation. Both naftopidil and prazosin activated caspase-3 and -8 in all the investigated malignant mesothelioma cells.Naftopidil, as well as prazosin, has the potential to induce apoptosis in malignant mesothelioma cells by activating caspase-8 and the effector caspase-3, regardless of α1-adrenoceptor blocking.
(Purpose) We report our early experience of laparoscopic radical prostatectomy for clinically localized prostatic cancer.(Material and Method) Between April and December 2000, 17 patients with clinical stage T1c to T2b prostatic cancer underwent laparoscopic radical prostatectomy. The median age was 70.9 year old, the median preoperative PSA and the median Gleason score of biopsy specimens was 7.1ng/ml, 6, respectively. We followed the operation technique from the “Montsouris technique”. Briefly, we used five trocars (two 10-mm and three 5-mm trocars) and the operation was performed transperitoneally. Pelvic lymph node dissection was performed in only one patient (case 3). Urethrovesical anastomosis was performed with 6 to 9 interrupted 3-0 absorbable sutures.(Results) No conversion to open surgery or reoperation was required in all cases. Median operation time was 450 minutes (range 290 to 750) and median intraoperative bleeding (including urine) was 600ml (range 100 to 3, 135). Only one case (case 3) needed homologous blood transfusion. Median postoperative Foley catheterization period was 9 days (range 5 to 19). Intraoperative complications related to operation procedure were one rectal injury and three vesical injuries, which were treated by absorbable suturing laparoscopically. Major complication was one complete A-V block (case 3) who was required a transient discontinuance of the procedure. Surgical margins were negative in 13 cases. Postoperative pathological evaluation was one pT0, five pT2a, seven pT2b and four pT3a. PSA value decreased less than 0.2ng/ml after surgery in all patients. Although six months have passed after the surgery in only 4 patients, all of them were fully continent.(Conclusion) Although the operation time is still longer than that of conventional open procedures, intraoperative magnified vision allows a more precise and safer dissection, especially for apical dissection. We believe that operative time will decrease with more experience. These results show that laparoscopic radical prostatectomy can be an acceptable treatment option for localized prostatic cancer.
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