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Biomedical subjects

S J Qiu

Publications and source records attributed to S J Qiu.

14 recordsLinked to original sources

Combined IL-12 and GM-CSF gene therapy for murine hepatocellular carcinoma.

Among various immunotherapeutic approaches, interleukin-12 (IL-12) is particularly appealing because of its superior antitumor effects, which have been demonstrated in preclinical as well as clinical studies. However, IL-12 therapy was often accompanied by severe side effects due mainly to the supranormal induction of interferon-gamma. To optimize the therapeutic efficacy and lower the side effects of IL-12, we have investigated the antitumor activity of combined IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene therapy in a highly malignant and poorly immunogenic murine hepatocellular carcinoma model. Using a versatile hydrodynamics-based DNA delivery method, we showed that the combined gene delivery of IL-12 and GM-CSF induced very strong antitumor cellular immunity and achieved significant therapeutic efficacy, whereas each cytokine gene alone yielded appreciable but less effects. We also observed that the combined therapy induced lower levels of interferon-gamma than did IL-12 alone. These results suggest that combined IL-12 and GM-CSF therapy can render a stronger antitumor effect as well as lowering potential side effects.

Animals↗

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein.

AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P < 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.

Adult↗

In vivo diffuse damage in human vertebral trabecular bone.

Accumulation of microdamage in vivo may lead to loss of bone quality. Until recently, linear microcracks were the only known form of in vivo microdamage, but through the use of confocal microscopy an additional level of damage (diffuse damage) has been identified. In this study, in vivo diffuse damage was characterized and quantified in human vertebral trabecular bone as a function of tissue morphology, age, race, gender, and previously quantified in vivo linear microcracks. Presence of diffuse damage in human vertebral tissue was confirmed and validated by simultaneous use of polarized, ultraviolet, and laser confocal microscopy. Diffuse damage was found to occur preferentially within trabecular packets rather than in interstitial bone (p < 0.05). It was consistently higher in men compared with women (p < 0.05), but was not different by race or age group. Diffuse damage did not correlate with linear microcracks, but both exhibited the same probability distribution in which the percentage of individuals having a particular amount of damage decreased exponentially as damage content increased. These findings suggest that diffuse damage accumulation and repair are governed by the same biological phenomena as microcracks, but diffuse damage contributes independently to the microdamage content of bone.

Adult↗

The expression of the mdm2 gene may be related to the aberration of the p53 gene in human hepatocellular carcinoma.

The relationship between mdm2 gene expression and p53 gene mutation in hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the disease were investigated in this study. Either the expression level of the mdm2 gene or the mutation rate of the p53 gene was higher in HCC than in paratumor liver tissues. Studies on the relationship between mdm2 and p53 revealed that mdm2 gene expression in HCC without p53 mutation was higher than when there was p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was found in the other 11 patients, and only 1 patient was found to have both mdm2 overexpression and p53 mutation. These results indicated that either mdm2 overexpression or p53 mutation may be related to the invasiveness of HCC. Considering that an autoregulatory feedback loop between the mdm2 and p53 genes may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53 protein. These results also suggest that mdm2 may be related to the high invasiveness of HCC through inactivating the tumor-suppressor function of the p53 gene.

Adult↗

Improved survival with resection after transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma.

AIM: This retrospective study was undertaken to analyze the outcome of hepatic resection in hepatocellular carcinomas (HCCs) that shrunk after transcatheter hepatic arterial chemoembolization (TACE) in 65 patients with unresectable HCCs between June 1987 and September 1996. MATERIALS AND METHODS: Among these 65 patients, the median diameter of the tumor was 9.9 cm (5.6-20.0) prior to the first TACE, after 1-6 times of TACE (median 3) the median tumor diameter reduced to 3.7 cm (1.9-12.5) prior to resection. The duration between the last TACE treatment and sequential resection varied from 1 to 9 months (median 2.5). Serum alpha-fetoprotein (AFP) levels were abnormal in 39 out of the 65 patients. In AFP producing HCCs, the AFP level returned to normal (</=20 microgram/l) in 14 out of 39 patients (35.9%). Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in 61 patients, right hemihepatectomy in 1, left trisegmentectomy in 2, and left hemihepatectomy in 1. RESULTS: Tumor necrosis ranged from 40 to 100% and pathologically and complete tumor necrosis occurred in 11 patients (16.9%). Of 14 patients with AFP levels decreased to normal, 10 still had microscopic living tumor foci. The 1-, 3- and 5-year survival rates of the 65 patients were 80.0, 65.0 and 56.0% respectively. CONCLUSION: TACE treatment can provide a chance of tumor resection for those patients with initially judged unresectable HCCs, and liver resection should be performed when the tumor has shrunk to be resectable, even when the AFP level has returned to normal.

Adult↗

Bone remodelling after internal fixation with different stiffness plates: ultrastructural investigation.

Forty adult New Zealand rabbits were used in this experiment. Four rabbits served as control and the rest 36 being divided into 3 groups, each of which was fixed respectively with methylmethacrylate, titanium alloy and stainless steel plate on the left intact tibiae. The cortical bone beneath the plate was harvested at 2, 4, 8 and 12 weeks after operation and observed by means of using transmission electron microscope. The major ultrastructural changes after internal fixation with different stiffness plates were alteration of osteocyte life cycle, perilacunar matrix and disorder of osteoblast and osteoblast coupling. The greater the stiffness of the plate, the greater the ultrastructural change.

Alloys↗

Repair of regional osteoporosis after removal of rigid fixing plate. An experimental investigation.

Twenty-four New Zealand white rabbits were plated on their intact left tibiae with stainless steel plates and 4 animals served as controls. The plates were removed 2 months after implantation in 20 plated animals. Of them, 4 were sacrificed immediately after plate removal and the other 16 were killed in successive groups with 4 in each group 1,2,3 and 4 months after plate removal respectively. The remaining 4 plated animals were killed at 6 months after implantation. Bone samples under the plates were harvested and prepared for polarized light microscopy to investigate the repair of the regional osteoporosis induced by rigid implant. The results indicated that the regional osteoporosis could recover gradually after plate removal. The repair process manifested itself mainly as the repair of resorption cavities and the remodeling of collagen fibers. The orientation of the collagen fibers remained disorganized when the resorption cavities had been repaired. It is suggested that delayed restoration of bone structure might be one of the potential causes of refracture after removal of the rigid implant.

Animals↗

Treatment of intra-articular fractures with shape memory compression staples.

The management of intra-articular fractures remains difficult. Shape memory compression staples fulfil nearly all the special treatment requirements of intra-articular fractures. Early bone union and 93.5 per cent satisfactory function were achieved in a series of 121 cases. Stable fixation, 'early' movement and continuous compressive force produced by the staple are the main factors contributing to good results.

Adolescent↗

The arch structure of trabeculae in normal femoral head and its biomechanical significance.

The microstructure of the normal human femoral head was observed under light and electron microscope. Most of the trabeculae were seen in the form of arch structure, and the collagen fibers and mineral columns among the trabeculae were arranged in different directions. These findings provide a new explanation of the mechanism by which the femoral head can bear high stress without collapse.

Adolescent↗

[The arch structure of trabeculae in normal femoral head and its biomechanical significance].

The microstructure of normal femoral head of human was observed under light and electron microscope. Most of the trabeculae were seen in the form of arch structure, and the collagen fibers and the mineral columns of trabeculae were arranged in different directions. This finding provides a new explanation of mechanism that femoral head can bear high stress without collapse.

Biomechanical Phenomena↗

[Ultrastructural investigation of experimental fracture healing: effect of fixation with plates of various materials].

The right tibiae of 45 new zealand rabbits were osteotomized and internally fixed with plate of methylmethacrylate (MMA) or stainless steel (SS) with or without compression. The animals were divided into 3 groups, 15 in each. The ultrastructure of the specimens are as follows. Repair of the fractures immobilized with MMA plate went through a typical course of secondary healing, showing obvious periosteal, contact and medullary callus. The fibroblasts, chondroblasts and osteoblasts were numerous and very active throughout the healing period, demons treating an extremely active synthesis and secretion function. Findings in fractures fixed with SS plate without compression manifested atypical secondary healing. The early callus was mainly of contact and medullary one, the periosteal callus set in rather late. The fibroblasts were active, but not the osteoblasts, and even less in some chondroblasts. Fractures fixed with SS plate with compression healed primarily on the plate side, while the opposite side showed fissure healing, like that without compression. Intramedulla repair looked similar to that of fissure healing. Although the fibroblasts and osteoblasts were much like that in the group without compression, no chondroblasts came into action. All these biological differences are supposed to be response to the magnitude of stress at the fracture site.

Animals↗

[Quantitative histologic study of early osteoporosis induced by plate fixation].

Thirty New Zealand rabbits were used in the experiment. Three animals served as control and the other 27 were divided into 3 groups, in which the tibiae of the animals were fixed by methylmethacrylate, titanium, and stainless-steel plates respectively. 4, 8, and 12 weeks after operation, 3 animals in each group were killed. Image analysis of microsection of the cortical bone beneath and opposite the plate was performed by a digital image processing system. All of the 3 types of plates may lead to bone loss, which is proportional to the degree of the stress protection produced by the plate. In addition, the amount of bone loss in each group was all much greater beneath the plate than opposite it.

Animals↗

An approach for difficult hepatectomy--retrograde hepatectomy in 29 patients with liver malignant tumor.

BACKGROUND/AIMS: Resection remained the best treatment for malignant liver tumor. However, it is difficult to resect a tumor which is huge and tightly invaded or adhered to the surrounding organs by classical procedures because of poor exposure. The purpose of the present study was to verify that retrograde hepatectomy was an acceptable approach. METHODOLOGY: Retrograde hepatectomy means that the operative procedure is reversed as compared with classical methods. Transection of the liver parenchymal was performed first, isolating adhesions between the resected liver and diaphragm or partial phrenectomy followed, and then after cutting corresponding ligaments, the liver tumor was removed. If the adjacent organs were invaded or adhered too tightly to be separated, they were removed with the resected liver. This approach was adopted in 29 patients with liver malignancy (group A) for difficult hepatectomy from June 1994 to June 1997. In the same period, classical hepatectomy was performed in 13 patients used as a control group (group B). The differences between these two groups were analyzed. RESULTS: When group A was compared with group B, the operative mortality was 0% versus 7.7% (p > 0.05), the operative time was shorter, being 175.9 +/- 49.7 min (range: 150-250 min) versus 251.9 +/- 66.9 min (range: 180-360 min) (p < 0.05), the estimated intra-operative blood loss being 1430.0 +/- 807.6 ml (600-4200 ml) versus 2907.7 +/- 1497.9 ml (800-7000 ml) (p < 0.05), and the incidence of post-operative complications was lower (p < 0.05). CONCLUSIONS: Retrograde hepatectomy is an alternative method to classical hepatectomy and suitable for resection of localized huge liver tumor when the exposure is inadequate by classical approach, particularly when the tumor adheres or invades closely to the diaphragm and/or the surrounding structures.

Adult↗

Complete resection of the caudate lobe of the liver with tumor: technique and experience.

BACKGROUND/AIMS: To study the technique and curative effects of complete resection of the caudate lobe of the liver with tumors. METHODOLOGY: There were 18 patients with tumors in the caudate lobe of the liver in this study. Among them, hepatocellular carcinoma was found in 12 patients, metastasis to the caudate lobe two years after resection of rectal carcinoma in one, cholangiocarcinoma in one, and huge benign tumor in four. Complete caudate lobectomy and combined with left lateral lobectomy or left hemihepatectomy or left trilobectomy were performed in this series. RESULTS: The median operating time was 227 min and median blood loss was 1590 mL, and the median blood transfusion was 1520 mL. No operative or postoperative mortality, or any postoperative complications were found in any of the patients. The 1-, 3- and 5-year survival rates of the 12 patients with hepatocellular carcinoma were 58.3%, 55.5% and 37.8%, respectively. One patient with cholangiocarcinoma died in postoperative 4 months. One patient with metastatic rectal cancer has been alive for more than 5 years after the operation, and 4 patients with benign tumors are still alive and well. CONCLUSIONS: Complete resection of the caudate lobe of the liver should be the first choice for removal of huge tumors originating from the caudate lobe, although this procedure is quite difficult and has a high risk factor.

Adult↗