Search

Vascular endothelial growth factor (VEGF) and its receptors play an important role in tumor progression; however, there is no report regarding this factor in uterine sarcoma. Thirty-nine patients with uterine sarcoma, 14 carcinosarcomas, 4 endometrial stromal sarcomas, and 21 leiomyosarcomas, were studied. By immunohistochemical staining, VEGF was not detected in normal uterine smooth muscle, but VEGF receptor-1 (flt-1) and VEGF receptor-2 (flk-1) were observed in 14 and 4 of 14 normal smooth muscles, respectively. Of 39 sarcomas, 25 expressed VEGF, and 38 and 34 sarcomas expressed flt-1 and flk-1 at various intensities, respectively. The staining intensity of VEGF, flt-1, and flk-1 was significantly higher in sarcoma than in normal uterine smooth muscle, but that of phospho-flt-1 (p-flt-1) was significantly lower in sarcoma than in normal uterine smooth muscle. When sarcomas were divided into two groups according to staining intensity, a significant difference in survival curves was observed in only p-flt-1 of leiomyosarcoma (P = 0.008), and in all sarcomas, a lower survival curve was also observed in the high staining intensity group than in the low staining intensity group, although there was no significant difference (P = 0.102). In conclusion, VEGF and its receptors are suggested to be involved in progression of uterine sarcoma, but only the p-flt-1 level significantly affected the survival of leiomyosarcoma patients.

Background Little is known of the fibrinolytic host immune mechanisms responsible for induction of chronic allograft nephropathy (CAN), defined as a loss in glomerular filtration rate (GFR) caused by tubular atrophy and interstitial fibrosis, often with fibrous intimal thickening in the small arteries. However, chronic rejection has been reported to be associated with decreased activity of the fibrinolytic system. In our previous study, [Deamino-Cys 1 , d -Arg 8 ]-vasopressin (dDAVP) induced urokinase-type plasminogen activator (uPA) release from human peripheral T lymphocytes via arginine vasopressin (AVP) V 2 -receptor-mediated reaction enhanced by an AVP V 1 -receptor antagonist. Therefore, we examined the level of uPA released from peripheral T lymphocytes by AVP in transplant patients with CAN in comparison with control groups. Patients and Methods In this study, we evaluated in vitro uPA releasing activity of lymphocytes obtained from renal allograft patients with well-functioning grafts (n = 9), CAN (n = 5), or acute rejection episodes (n = 5) compared with lymphocytes from healthy volunteers with normal renal function (n = 12) or patients with renal insufficiency (n = 5). Results Lymphocytes prepared from patients with chronic allograft nephropathy showed a significantly lower increase in uPA release induced by the combination of the V 1 -receptor antagonist and dDAVP compared with those from the other groups. Conclusion This finding suggested that a decrease in uPA release from human peripheral blood lymphocytes by AVP-related peptides may be potentially involved in the pathophysiology of CAN.

The role of activated T cells in graft arteriosclerosis, which is observed in chronic renal allograft nephropathy, and the involvement of major histocompatibility complex (MHC) incompatibility remain to be determined. We examined the effect of T lymphocytes that were obtained from renal transplant patients undergoing chronic rejection treated with cyclosporine (CsA) on platelet-derived growth factor (PDGF)-induced proliferation of cultured human vascular smooth muscle cells (SMC) and compared the proliferation activity of T lymphocytes with MHC incompatibility, especially DRB 1 mismatch.Renal transplant patients with continued allograft function, who survived more than 1 year after transplantation, were recruited. Chronic rejection was documented by graft-biopsy findings together with increasing serum creatinine levels (10-20% per year). After the incubation of supernatant (conditioning medium) of cultured T cells from CsA-treated renal transplant patients with chronic rejection (n=18) and with normal renal function (n=14) as control, normal subjects (n=11) and chronic hemodialysis (HD) patients (n=5) with cultured SMC in the presence or absence of PDGF, DNA synthesis (3H-thymidine uptake) of SMC was examined. The in vitro effects of CsA on DNA synthesis of cultured SMC were also evaluated.The supernatant of cultured T cells from renal transplant patients with chronic rejection stimulated PDGF-induced DNA synthesis of SMC in a dose-dependent manner, showing significant enhancement as compared with control transplant patients, normal subjects, and chronic HD patients. The supernatant itself did not significantly stimulate DNA synthesis of SMC. No significant in vitro stimulation of CsA on DNA synthesis was observed. The supernatant of T cells obtained from recipients undergoing chronic rejection with two DRB 1 mismatches showed significantly higher enhanced activity of PDGF-induced DNA synthesis than the supernatant from those recipients without mismatch of DRB 1. On the other hand, no significant correlation of the enhanced activity by T cell supernatant to HLA A and B mismatch numbers was observed.Growth factor-promoting factors(s) derived from activated T cells associated with MHC class II DR expression, which promotes PDGF-induced proliferation of SMC, exists in renal transplant patients with chronic renal allograft nephropathy, and is probably involved in arteriosclerosis of the graft kidney.

Cervical carcinomas develop as a result of multiple genetic alterations, and specific alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p is one of those most frequently involved in a loss of heterozygosity (LOH) in patients with cervical carcinoma. The aim of this study was to identify the correlation between the LOH on chromosome 6p21.2 and the recurrence of cervical cancer after radiotherapy. A total of 62 patients with cervical cancer (stage I, 4 patients; stage II, 9 patients; stage III, 37 patients; and stage IV, 12 patients) were included in this study. All patients were treated with definitive radiotherapy. We analyzed specimens from the tumors and venous blood of all patients. Tumors and normal DNA were analyzed by PCR for genetic losses at three polymorphic microsatellite loci (D6S276, D6S1624, and D6S1583). Chromosome 6p21.2 is involved in the LOH in 46.8% (29 of 62) of the informative carcinomas. Ten patients had a local recurrence, 4 had distant metastases, and 13 had both local recurrence and distant metastases after radiotherapy. To evaluate the relationship between the recurrence after radiotherapy and LOH on chromosome 6p21.2, we divided the patients into those with cancer recurrence (n = 27) and those without recurrence (n = 35). LOH on chromosome 6p21.2 was correlated with recurrence after radiotherapy (P = 0.006). The tumors in patients with recurrence were significantly larger than those in patients without recurrence (P = 0.003). However, there was no correlation between the sizes and stages of tumors and the LOH on chromosome 6p21.2. In addition, both overall survival and relapse-free survival were significantly worse for the patients with LOH as compared with those without LOH (P = 0.02 and P = 0.002, respectively). The results of this study suggest that LOH on 6p21.2 is correlated with recurrence of cervical carcinoma after radiotherapy.

The objective of this study was to clarify the relationship between the serum level of the Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) and the clinical features including sex, age, Child's classification, virus markers, tumour size, tumour stage, distant metastasis, histopathologic findings, portal thrombus and outcome of hepatocellular carcinoma (HCC). We measured the AFP-L3 levels in 170 HCC cases at the time of diagnosis using lectin-affinity electrophoresis followed by antibody-affinity blotting. The patients were divided into two groups, those who were AFP-L3 positive (n=56; AFP-L3 >/=15% relative to the total alpha-fetoprotein (AFP) concentration) and those who were AFP-L3 negative (n=114; AFP-L3

Fifty-nine methacarn-fixed, paraffin-embedded human breast carcinomas were immunostained by QB-END/10 (an antibody to CD34 antigen) to observe microvessels and by PC10 (an antibody to proliferating cell nuclear antigen; PCNA) to determine tumor cell proliferation; 9 normal human breast tissue specimens were also immunostained by QB-END/10. The number of microvessels in the periphery of the breast carcinoma was significantly greater than both that in the center of the breast carcinoma and that in the normal breast. There was also a significant relationship between the number of microvessels in the periphery of breast carcinomas and the histological tumor size and lymph node status. However, there was no significant relationship between the tumor cell proliferation activity (PCNA positive cell ratio) and any clinical or histopathological variables. The number of microvessels and the tumor cell proliferation activity showed a weak negative correlation.

To evaluate the effects of dietary fats on breast cancer growth and metastasis, KPL-1 human breast carcinoma cells which have a propensity for axillary lymph node metastasis when inoculated into the thoracic mammary fat pad of female nude mice were examined. The mice were fed one of three semipurified diets containing 9.5% eicosapentaenoic acid plus 0.5% linoleic acid (EPA diet), 10% linoleic acid (LA diet), or 9.5% palmitic acid plus 0.5% linoleic acid (PA diet), or commercial laboratory chow containing 8.5% fat of which 4.1% was LA, 1.1% was PA, 0.06% was EPA, and 3.24% was other (Standard diet) starting 19 days before tumor cell inoculation and continuing until the end of the experiment (43 days after tumor cell inoculation). The tumor growth was faster and at a higher incidence in the mice fed the LA diet, and much slower and at a lower incidence in the EPA diet group compared with the mice fed the PA or Standard diet; the two separate experiment demonstrated identical results. The differences in tumor weight between the LA and PA groups and between the PA and EPA groups were significant (P0.05, respectively) at the termination of the experiment; the differences were due to different tumor cell proliferation rates. In an in vitro MTT assay, fatty acids showed direct stimulatory or inhibitory effects on the KPL-1 cells. Lymph node metastasis was seen in the LA and Standard diet groups, whereas it was not seen in the PA or EPA groups. The body weights were significantly lighter in the LA and EPA groups compared with the PA and Standard diet groups (P0.05, respectively). The results indicate that the EPA diet produced a reduction in tumor cell growth and metastasis whereas the LA diet had an enhancing effect on these parameters; dietary fatty acids may thus have a direct role in the growth and metastasis of human breast carcinoma independent of their systemic effects.

Synovial sarcoma with pulmonary metastases appeared to be sensitive to multiagent chemotherapy of Pirarubicin, Ifosfamide, and Vincristine Sulfate. However, this chemotherapy regimen could not be continued because of severe hemorrhagic cystitis due to the toxicity of Ifosfamide. Even in the advanced stage, this multiagent chemotherapy would be useful for the treatment of synovial sarcoma, if hemorrhagic cystitis could be prevented.

The relationship between genotypes of HLA-DRB 1 alleles and the progression of bone destruction of RA patients was assessed. The genotypes of the HLA-DRB 1 alleles were determined in 329 Japanese patients with seropositive RNA by polymerase chain reaction and allele-specific oligonucleotide probe techniques. We regarded HLA-DRB 1* 0101, 0401, 0404, 0405, 1001 and 1402 as susceptible alleles of RA and classified the patients into three groups. The s/s group consisted of those with susceptible factors in both of the HLA-DRB 1 alleles. The s/n group was made up of those having one susceptible factor and one non-susceptible factor. The n/n group consisted of those possessing two non-susceptible factors. The grading of radiographic change that was evaluated by Larsen's criteria compared with the genotyped results. In the result, the median years taken to development to grade III, IV and V were significantly shorter in the s/s groups compared with that in the s/n and n/n groups. Thus, genotyping of HLA-DRB 1 can be a useful prognostic market in the progression of bone destruction of RA.

Six post-operative cancer patients receiving chronic dialysis (4 colorectal and 2 gastric cancer) were given daily UFT (300 mg/day tid). To determine the clearance of UFT with dialysis, the plasma concentration of tegafur, 5-FU and uracil were measured on the day with dialysis and without dialysis. The plasma concentrations of tegafur at 2 hours after oral administration of UFT showed no difference between the day with dialysis and without dialysis. The concentration of 5-FU on the next day with dialysis was almost same as that of the patients with normal renal function because of the clearance of 5-FU with dialysis, although that on the 2nd day after dialysis was higher than that with dialysis. It was difficult to compare the plasma concentrations of uracil, because they are different in each patient. Therefore, it was considered to be difficult to maintain the suitable plasma concentration of uracil. However, clearance of UFT with dialysis was good and no severe side effect was observed in administration of UFT. These data suggest that UFT can be useful drug for gastrointestinal cancer patients receiving dialysis in a post-operative adjuvant chemotherapy.

We describe a simple bone cyst in a patient who had an osteoblastic lesion which had been discovered 1 1/2 years earlier. Curettage and drilling proved effective treatment. We suggest that increased regional blood flow, in association with bone formation, produces a hydrodynamic disorder followed by venous obstruction leading to the formation of a bone cyst.

We reported two cases of thymic cyst which were accidentally found by chest X ray. On CT, they showed near water low density masses with thin walls, situated in the prevascular space. In the case 2, the septum-like structure was found by MRI, however, it was not clear by CT.

Transcatheter chemo-embolization (TCE) in hepatocellular carcinoma (HCC) was performed in 38 patients. The patients were examined by MR imaging before TCE as well as one week and 4 to 5 weeks after TCE. The tumor signal intensity in T2 weighted images increased in 13 cases and decreased in 19 cases after TCE. Increased intensity seemed to reflect intra-tumoral hemorrhage or liquefaction accompanying tumor necrosis. Decreased intensity seemed to reflect coagulation necrosis. In 9 of 18 cases followed over a 2-month period the signal intensity had decreased in both T1 and T2 weighted images. In these patients the tumor showed no recurrence at angiography and the decreased signal seemed to reflect the completion of coagulation necrosis. A hyper- and/or hypointense rim around the tumor appeared in 22 cases. These changes were thought to be perifocal edema or granulation tissue around the tumor. MR imaging was useful in evaluating the necrotic process of the tumor after TCE.

The Tl-201 Cl time activity curves were evaluated in 17 patients with histologically proven benign nodules and papillary carcinoma of the thyroid gland. In the dynamic studies, the uptake at the region of interest was counted every 10 sec for 20 min after the intravenous injection of 2mCi Tl-201 Cl. The curves from frame 21 to 100 were transformed to linear plots for clinical evaluation. Papillary carcinoma could not be differentiated from benign lesions by means of the values of the washout rate. However, the "relative washout rate" in papillary carcinoma was lower than that of benign lesions (P less than 0.05). Although the average values of the "relative extrapolated uptake" in papillary carcinoma appeared to be greater than those in benign lesions, the difference was not statistically significant. The difference in the washout rates between lymph node metastases and local recurrences, and pulmonary metastases of the papillary carcinoma was significant (P less than 0.05).

Transcatheter chemo-embolization (TCE) for hepatocellular carcinoma (HCC) was performed on 31 patients, and on 4 of the 31 patients, it was performed twice. The patients were examined by MR both before TCE and after TCE (1 week and 4-5 weeks respectively). On MR images, the change of the tumor signal intensity was classified into 3 groups. In group 1, (G1, 8 cases), obvious change of intensity was seen in the whole tumor. In group 2, (G2, 10 cases), it was seen in some parts of the tumor and in group 3, (G3, 17 cases), only a very slight change of intensity was seen in the whole tumor. In G1 and G2, the rate of AFP decrease was remarkable, but in G3, it was very slight. In G1 and G2, the change of the tumor signal intensity was divided into 2 types on a T2 weighted image. One, is the increase of the intensity, (6 cases). The other, is decrease of intensity, (12 cases). The former seemed to reflect the intra-tumoral hemorrhage accompanying tumor necrosis, the latter, seemed to reflect the coagulation necrosis. The ring of low and high intensity around the tumor appeared anew in 11 cases, and in 2 cases, it increased in size. These changes which have never been recognized on CT images, were thought to be a granulation tissue around the tumor. The influence of the accumulated lipiodol is slight for the change of intensity on the tumor.

To evaluate the common belief that cancer metastasis to adrenocortical adenomas is a predilected phenomenon, we compared the real incidence of cancer metastasis obtained by analyzing the autopsy results of our 160 lung cancer cases, as well as those found by reviewing the literature, with the theoretical incidence obtained through the simulation models we made. The results disclosed that statistically, the real incidence was significantly higher than the theoretical probability. Therefore, we concluded that the metastasis of lung carcinoma to adrenocortical adenomas is indeed predilected.

Internal pressure of simple bone cyst was slightly higher than normal bone marrow pressure measured on contralateral side. Internal pressure of the cyst measured during drill-holing with Kirschner wire gradually decreased along with the increase in the number of drill-holes. Internal PO2 was markedly lower than PO2 of venous and arterial blood measured synchronously. Venous obstruction in bone may be an etiology of simple bone cyst. Follow up study showed that all cysts of six cases treated by the multiple drill-hole method were filled up with bony tissue within five months after the treatment, and the clinical result of the treatment was excellent. Multiple drill-hole method may be the first choice in the treatment of simple bone cyst in the younger patients, because the operative invasion of this method was minimum.