Prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice.

Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.

Association between the Temporomandibular Joint Morphology and Chewing Pattern.

This study aimed to investigate whether the morphology of the temporomandibular joint (TMJ) is associated with chewing patterns while considering skeletal morphology, sex, age, and symptoms of temporomandibular disorder (TMD). A cross-sectional observational study of 102 TMJs of 80 patients (age 16-40 years) was performed using pretreatment records of cone-beam computed tomography imaging of the TMJ, mandibular kinesiographic records of gum chewing, lateral and posteroanterior cephalometric radiographs, patient history, and pretreatment questionnaires. To select appropriate TMJ measurements, linear regression analyses were performed using TMJ measurements as dependent variables and chewing patterns as the independent variable with adjustment for other covariates, including Nasion-B plane (SNB) angle, Frankfort-mandibular plane angle (FMA), amount of lateral mandibular shift, sex, age, and symptoms of TMD. In multiple linear regression models adjusted for other covariates, the length of the horizontal short axis of the condyle and radius of the condyle at 135° from the medial pole were significantly (p < 0.05) associated with the chewing patterns in the frontal plane on the working side. "Non-bilateral grinding" displayed a more rounded shape of the mandibular condyle. Conversely, "bilateral grinding" exhibited a flatter shape in the anteroposterior aspect. These findings suggest that the mandibular condyle morphology might be related to skeletal and masticatory function, including chewing patterns.

Comparison of Osteoconductive Ability of Two Types of Cholesterol-Bearing Pullulan (CHP) Nanogel-Hydrogels Impregnated with BMP-2 and RANKL-Binding Peptide: Bone Histomorphometric Study in a Murine Calvarial Defect Model.

The receptor activator of NF-κB ligand (RANKL)-binding peptide is known to accelerate bone morphogenetic protein (BMP)-2-induced bone formation. Cholesterol-bearing pullulan (CHP)-OA nanogel-crosslinked PEG gel (CHP-OA nanogel-hydrogel) was shown to release the RANKL-binding peptide sustainably; however, an appropriate scaffold for peptide-accelerated bone formation is not determined yet. This study compares the osteoconductivity of CHP-OA hydrogel and another CHP nanogel, CHP-A nanogel-crosslinked PEG gel (CHP-A nanogel-hydrogel), in the bone formation induced by BMP-2 and the peptide. A calvarial defect model was performed in 5-week-old male mice, and scaffolds were placed in the defect. In vivo µCT was performed every week. Radiological and histological analyses after 4 weeks of scaffold placement revealed that the calcified bone area and the bone formation activity at the defect site in the CHP-OA hydrogel were significantly lower than those in the CHP-A hydrogel when the scaffolds were impregnated with both BMP-2 and the RANKL-binding peptide. The amount of induced bone was similar in both CHP-A and CHP-OA hydrogels when impregnated with BMP-2 alone. In conclusion, CHP-A hydrogel could be an appropriate scaffold compared to the CHP-OA hydrogel when the local bone formation was induced by the combination of RANKL-binding peptide and BMP-2, but not by BMP-2 alone.

Difference in apical resorption activity during rat molar root formation in response to mechanical force.

OBJECTIVE: To investigate whether there is a difference in apical resorption activity during the development of roots in response to mechanical force in vivo. METHODS: Maxillary first molars (M1) from postnatal day (PN) 21 and PN35 male rats were selected as representatives of the root-developing and root-completing groups, respectively. A mechanical force of 3 cN was applied to M1 on PN21 and PN35, and the maxilla was collected on PN28 and PN42. Odontoclastogenesis and root morphology were investigated using micro-focus X-ray computed tomography, followed by immunohistochemistry and quantitative real-time polymerase chain reaction to clarify root resorption activity. RESULTS: Development of the mesiobuccal root (MBR) preceded the mesial root (MR). In the PN28 force application (FA) group, the dentine was bent, but the histology, including Hertwig's epithelial root sheath (HERS), was intact. No odontoclasts and resorption lacunae were found in the apical area of the MRs, and only lateral root resorption was observed. External apical root resorption (EARR) was observed in the MR of PN42 (FA) and in the MBR of both PN28 (FA) and PN42 (FA). The expression of osteopontin changed accordingly. No significant change occurred in osteoprotegerin or receptor activator of nuclear factor-κB ligand expression in the MRs of the PN28 (FA) group. LIMITATIONS: Our animal model did not adequately simulate the clinical process of tooth movement in humans. CONCLUSIONS: Force application delayed HERS dissociation on the compression side of the developing roots, leading to inhibitory effects on cementogenesis, which resulted in decreased odontoclast differentiation and prevention of EARR.

Effects of short-term orthodontic force application on the root at different developmental stages in rat maxillary molars.

INTRODUCTION: The suitable timing and duration of orthodontic force to be applied to teeth with developing roots are unclear. We investigated the effects of short-term orthodontic force application on the roots at different root developmental stages in rats to predict the optimal timing for orthodontic treatment of teeth with developing roots. METHODS: Light orthodontic force was applied on the maxillary first molars of rats from postnatal day (PN) 21 or PN28 for 3 days. After that, the force was released, and the roots were evaluated on PN35 to determine the root length, apical morphology, and cell proliferation of the maxillary first mesial roots using microcomputed tomography and histologic evaluation. RESULTS: When a light orthodontic force was applied from PN21, the root length did not differ from that in age-matched controls. In addition, after the force was released, the roots attained the normal root-completing length and had a well-formed root apical morphology at PN35. Conversely, when the force was applied from PN28, the roots showed apical abnormalities characterized by deformed dentin and disorganized arrangement of odontoblasts, reduced apical cell proliferation, and significantly shorter length than those in the age-matched controls at PN31. The shortened root and disturbed apical integrity could not be rescued by releasing the orthodontic force at PN35. CONCLUSIONS: Short-term orthodontic force at the late and slow root developmental stage results in a shortened root and a defect in the root apex with reduced cell proliferation. Our findings support that orthodontic force for a limited duration during the active and rapid root developmental stage is more favorable than during the late and slow stage.

A pilot study to investigate the histomorphometric changes of murine maxillary bone around the site of mini-screw insertion in regenerated bone induced by anabolic reagents.

OBJECTIVE: The objective of this study was to investigate the histomorphometric changes around the site of mini-screw insertion in the regenerated bone which was induced by an anabolic-injection method using both anabolic peptide and bone morphogenetic protein 2 (BMP-2). METHODS: Twenty-seven eight-week-old C57BL/6J male mice were used. Some mice received submucosal co-injections of anabolic peptide and BMP-2 just in front of the maxillary first molar. Screw insertion was then performed 4 weeks after injection. All mice underwent a weekly in vivo micro-focal X-ray computed tomography (µCT) analysis before being sacrificed at week 8. The bone formation activity was evaluated using fluorescent labelling in the undecalcified sections. The analyses, including screw insertion, were performed in the frontal plane, in front of the site of screw insertion. RESULTS: Reconstructed µCT images revealed that the co-injection of anabolic reagents could lead to a gradual increase in the bone mineral density (BMD) of the injection-induced thickened bone by week 8. Both radiological and histomorphometric analyses indicated that screw insertion did not have any deleterious effects on either the BMD or the bone formation activity of the induced bone. Furthermore, the injection of anabolic reagents also led to an increase in the BMD of the underlying maxillary bone at the injection site. CONCLUSION: Our histomorphometric analyses suggest that performing such anabolic injection to thicken bone could stimulate bone formation in the basal bone as well as in the induced bone. Similar augmentation of bone formation could be obtained even after subsequent screw insertion at the site of the induced bone.

Evaluating the morphological features of the lateral pterygoid insertion into the medial surface of the condylar process.

OBJECTIVE: The lateral pterygoid is vital in coordinating multidimensional jaw movements. Since a vector in three-dimensional (3D) space is defined by two 3D points, the role of the lateral pterygoid in 3D jaw movements is defined by its origin and insertion. Reportedly, the lateral pterygoid is inserted into not only the pterygoid fovea but also into the medial surface of the condylar process. The objective was to investigate the morphological features of the region of the lateral pterygoid that inserted into the medial surface of the condylar process. MATERIAL AND METHODS: Ten head halves of seven cadaveric donors were analyzed. In all specimens, the insertion area on the medial surface of the condylar process was measured based on microcomputed tomography images. Muscle fibers were separated into ≥50 small bundles, and positional relationships between the origins and insertions were investigated. RESULTS: Overall, 28.8 ± 5.0% of the insertion area of the lateral pterygoid was situated on the medial surface of the condylar process. Moreover, muscle fiber arrangement revealed that origins of the muscle bundles inserting into the medial surface in seven specimens posteriorly occupied the lateral plate of the pterygoid process longitudinally, whereas those in three specimens mainly occupied the posteroinferior portion. CONCLUSIONS: Muscle bundle inserting on the medial surface of the condylar process had a broad insertion area and a distinct origin on the posterior region of the lateral plate of the pterygoid process. This muscle bundle could act as one of the significant subunits within the lateral pterygoid. Therefore, anatomical coordination mechanisms underlying jaw movement cannot be elucidated without considering this subunit.

Effects of mechanical force application on the developing root apex in rat maxillary molars.

OBJECTIVES: We aimed to investigate the effects of mechanical force application on the developing root apex in vivo. DESIGN: Mechanical force was applied on the maxillary first molars of Sprague-Dawley rats at postnatal day 21 for 1, 3, 5, and 7 days to induce tooth movement. We observed the developing root apex of the mesial root of first molar by using micro-focus X-ray computed tomography, histological staining, immunohistochemistry and in situ hybridization to analyze apical cell proliferation and gene expression. Moreover, the force was released after 3 and 7 days of tooth movement, and root apical morphology at postnatal day 35 was subsequently observed. RESULTS: After 1 and 3 days of tooth movement, root apical morphology was altered by increasing immune-reactivity of laminin in the forming periodontal ligament. After 7 days of tooth movement, the root length decreased significantly with bending root apex, decreased cell proliferation and altered gene expression in developing root apex. At postnatal day 35, apical morphology showed no obvious abnormality when the force was released after 3 days of tooth movement, whereas root apical bending was not rescued when the force was released after 7 days. CONCLUSIONS: Relatively short-term force application had no obvious adverse effects on the developing root apex. However, relatively long-term force application altered root apex by affecting Hertwig's epithelial root sheath morphology and apical cellular behavior.

Effects of continuous force application for extrusive tipping movement on periapical root resorption in the rat mandibular first molar.

OBJECTIVE: The purpose of this study was to clarify the effects of continuous force application for extrusive tipping movement and occlusal interference on periapical root resorption in the rat mandibular first molar. METHODS: We constructed an appliance comprising a titanium screw implant with a cobalt-chromium post as the anchorage unit and a nickel-titanium closed coil spring (50 cN) as the active unit. Force was applied on the mandibular left first molar of rats for 8 (n = 10) and 15 days (n = 10; experimental groups), with the tooth in occlusion. Five rats were included as a non-treated control group to examine the body effect of the appliance. Active root resorption lacunae, identified using tartrate-resistant acid phosphatase, were evaluated in terms of the length, depth, and area. RESULTS: The rat mandibular first molars were mesially tipped and extruded in the occlusal direction. This mesio-occlusal tipping movement and occlusion resulted in the formation of a compression zone and active root resorption lacunae in the distoapical third of the distal roots. However, there was no significant difference in the amount of root resorption between the two experimental groups. The control group did not exhibit any active root resorption lacunae. CONCLUSIONS: Periapical root resorption was induced by continuous extrusive tipping force and occlusal interference in rat mandibular molars. These data suggest that we orthodontists had better take care not to induce occlusal interference during our orthodontic treatment.

The relationships between the arrangement of teeth, root resorption, and dental maturity in bovine mandibular incisors.

OBJECTIVE: The objective of this study is to investigate the eruption pattern and root resorption of the bovine anterior dentition in relation to growth-related parameters based on dental maturity. METHODS: A cross-sectional study was conducted on 110 bovine anterior mandibles by using standard radiography, cone-beam computed tomography (CBCT), and actual measurements. We determined the relationships between the stages of dental maturity by using a modification of Demirjian's method and various growth-related parameters, such as the activity of the root-resorbing tissue and mobility of the deciduous teeth. The correlation of growth-related parameters with interdental spacing and distal unusual root resorption (DRR) of the deciduous fourth incisor was assessed. The cause of mesial unusual root resorption (MRR) of the deciduous fourth incisor was determined on the basis of the arrangement of the permanent third incisor. RESULTS: An independent t-test and chi-square test indicated significant differences in growth-related parameters associated with dental arch length discrepancy and factors related to the shedding of deciduous teeth between the low and high dental maturity groups. The samples with interdental spacing and DRR showed a larger sum of mesiodistal permanent crown widths and higher dental maturity than did the respective controls. Samples with MRR tended to show a lingually rotated distal tip of the adjacent tooth crown. CONCLUSIONS: Dental maturity has relevance to the interdental spaces and unusual root resorption of mixed dentition. The position of the adjacent tooth crown on CBCT may be correlated with the occurrence of unusual root resorption of the incisor.

Proinflammatory mediators related to orthodontically induced periapical root resorption in rat mandibular molars.

OBJECTIVES: The early phase of orthodontic tooth movement involves acute inflammatory response that may induce bone resorption. The aim of this study was to localize and quantify cells in the periodontium expressing proinflammatory mediators during orthodontically induced periapical root resorption of the rat mandibular molars. MATERIALS AND METHODS: The levels of proinflammatory cytokines interleukin-1 (IL-1) α and ß, tumor necrosis factor-α (TNF-α), inflammatory enzymes cyclooxygenase (COX) 1 and 2, and their product prostaglandin E2 (PGE2) in the root resorption site were compared to those in the corresponding area of the untreated periodontal ligament (PDL) of physiologically drifting teeth. Continuous heavy orthodontic force was applied to the mandibular first molar for 8 and 15 days while in occlusion to induce root resorption. Frozen sections including root resorption lacunae were analyzed for the activity of non-specific esterase (NSE) and tartrate-resistant acid phosphatase (TRAP) by enzyme histochemistry and for the expression of IL-1α, IL-1ß, TNF-α, COX-1, COX-2, and PGE2 by immunohistochemistry. RESULTS: The active root resorption lacunae had significantly more TRAP-positive multinucleated odontoclasts, whereas the number of NSE-positive cells of the monocyte-macrophage lineage did not differ from that in the control PDL. Several types of periodontal cells exhibited a significant increase in the expression of IL-1α, IL-1ß, TNF-α, COX-2, and PGE2 in the root resorption zone, while COX-1 was rarely detected. CONCLUSIONS: These data suggest that proinflammatory mediators expressed in periodontal cells may synergistically promote apical root resorption in response to continuous heavy mechanical force applied to teeth.

[A case of advanced gastric cancer with multiple liver metastases treated with preoperative TS-1/CDDP chemotherapy and resection, with a complete response and survival for 7 years].

CASE: An 82-year-old man died because of squamous cell carcinoma of the right lung with metastasis to the left femoral bone. At the age of 75 years, he was admitted to our hospital because of hematemesis. Widespread type 3 gastric cancer was detected in the lesser curvature. Computed tomography(CT)showed multiple liver metastases. Preoperative chemotherapy with TS-1/cisplatin(CDDP)was administered. TS-1 was orally administered at 80mg/body/day and CDDP was administered by intravenous infusion at 20mg/body/day every week for 3 weeks and this was followed by a drug-free 2-week period as the first course. After the fourth course, gastrectomy was performed for the primary lesion and radiofrequency ablation(RFA)was performed for the liver metastases. The patient survived for more than 7 years with a complete response (CR)and died thereafter because of squamous cell carcinoma of the lung.

Soft tissue cephalometric norms for orthognathic and cosmetic surgery.

PURPOSE: Proportionality of the lower and middle thirds of the face is a key determinant of successful orthognathic treatment. A flatter profile and marked variance of the soft tissue envelope in the Japanese population complicates the accurate assessment of these proportions. This study aimed to identify gender differences and establish norms for Japanese young adults using the method of soft tissue cephalometric analysis (STCA) by Arnett et al (Am J Orthod Dentofacial Orthop 116:239, 1999). MATERIALS AND METHODS: Lateral cephalograms of 49 young normal Japanese subjects (19 men, 30 women) were selected from the archival records and analyzed with STCA. The Student t test was used to compare mean values of the male and female groups. RESULTS: Significant differences were found between women and men. Men had a flatter occlusal plane and a more acute nasolabial angle than women. Men showed larger values for upper and lower lip thickness, menton soft tissue thickness, and vertical face length, especially in the lower third of the face. Women had a more projected midface than men. Compared with established STCA norms, the Japanese have more midfacial projection. CONCLUSIONS: Significant gender differences were found in the thickness, lower third length, and midface projection in Japanese young adults, which should be taken into account when interpreting measurements for orthognathic surgical planning. These differences can serve as norms for STCA in young Japanese adults. Differences were noted between the reference values of Arnett et al and Japanese subjects.

Development of a surgical procedure for biointegration of a newly designed orthodontic onplant.

AIM: An onplant is an orthodontic anchorage device fixed to the bone surface with osseointegration. Compared with implants, the onplant has fewer limitations regarding placement and is less invasive. The purpose of this study was to clarify the effect of bone-surface treatment and the fixing method of a newly designed smaller-sized onplant and establish a prospective surgical procedure for placement of the onplant. METHODS: Thirty-eight onplants were placed in six beagle dogs. The bone surface was planed where the cortical bone was thick and reducible (bone-planed). Where the cortical bone was thin and uneven, a filling was inserted in the space between the onplant and bone (filled). The onplant was fixed to the bone in one of two ways: using a membrane that covered the onplant and fixing the membrane with titanium pins (membrane-fixed) or fixing the onplant directly to the bone using the same titanium pins (pin-fixed). RESULTS: Twelve weeks later, all the onplants were osseointegrated. The bone-planed group showed significantly (P < .05) larger shear stress than the filled groups. In the bone-planed group, the pin-fixed group showed significantly (P < .05) larger shear stress than the membrane-fixed group. The shear stresses were considered strong enough to function in orthodontic treatment. CONCLUSION: The effect of the bone-surface treatment and the onplant-fixing method on the shear stress was clarified, and the findings in the present study may be useful for the improvement of surgical procedures for orthodontic onplants.

Preapplication of orthodontic forces to the donor teeth affects periodontal healing of transplanted teeth.

OBJECTIVE: To investigate how the preapplication of orthodontic forces to the donor teeth affects the periodontal healing after transplantation. MATERIALS AND METHODS: The orthodontic force (1.5 cN) was applied to the maxillary right molars of 6-week-old male Spraque-Dawley rats (n = 21) in the experimental side, and the left side of the same animals was used as the control. After 7 days, both right and left maxillary second molars were extracted or replanted. Periodontal conditions were evaluated in the histological specimens 7 days after applying orthodontic force (before and after extraction) and 14 days after replantation. RESULTS: The application of orthodontic force for 7 days significantly increased the periodontal ligament (PDL) space and also the width of the alveolar socket, which resulted in a rich attached PDL to the root surface of the extracted teeth. Significantly more root resorption was also detected in the control side without preapplication of orthodontic force 14 days after replantation. This root resorption might involve in the disruption of the PDL. CONCLUSION: These results suggested that the preapplication of orthodontic force to the donor teeth increased the PDL width and eased the extraction, which might decrease root resorption after replantation.

[A resected case of advanced gastric cancer with multiple liver metastasis responding to preoperative TS-1/CDDP chemotherapy].

CASE: A 75-year-old man was admitted to our hospital with hematoemesis. Gastrofiber-scopy revealed that type 3 gastric cancer was widespread in the lesser curvature. Multiple liver metastases 5 cm in diameter were shown on CT. We thought that the case was unresectable, and TS-1/CDDP chemotherapy was performed. TS-1 (80 mg/body/day) was orally administered and CDDP at 20 mg/body/day by intravenous drip infusion a week for 3 weeks followed by a drug-free 2 week period as the first course. After the third course, the primary lesion and the liver metastasis showed a partial response in terms of size. No serious drug adverse reaction was observed. Since there was no longer any reduction of the tumor, gastrectomy and coagulation therapy for liver metastasis were performed, and he has been alive for 15 months without recurrence. Combined use of TS-1 and CDDP is effective as neoadjuvant chemotherapy for advanced gastric cancer.

[The relationship between plasma level of VEGF or soluble Flt-1 and efficacy of hepatic arterial chemotherapy in patients with liver metastasis of colorectal cancer].

PURPOSE: To clarify the clinical significance of determining plasma levels of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in colorectal cancer, changes in plasma levels of VEGF and sFIt 1 during hepatic arterial chemotherapy were investigated in patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: The relationship between plasma level of VEGF or sFlt-1 and serum level of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), or the efficacy of hepatic arterial chemotherapy was investigated in patients with liver metastases of colorectal cancer (n=19). Plasma levels of VEGF and sFlt-1 were determined by the enzyme linked immunosorbent assay. RESULTS: There was a positive relationship between plasma level of sFlt-1 and serum level of CEA (p = 0.13). The other combinations did not show any statistical correlations. Also, in terms of the doubling time (DT), there was a positive relationship between the sFlt1-DT and the CEA-DT (p = 0.04). The levels of VEGF tended to change in accordance with the efficacy of chemotherapy. In contrast, plasma levels of sFlt-1 increased in patients with the progressive disease, whereas the levels did not decrease in patients with the partial response. CONCLUSIONS: These results suggested that (1) VEGF may be a useful tumor marker during the chemotherapy in patients, whose CEA and CA19-9 are below the cutoff, and (2) the shrinkage of liver metastases may not cause a decrease in sFlt-1 or the half-life of sFlt-1 may be considerably long.

A huge primary peritoneal papillary adenocarcinoma which demonstrated imaging findings similar to those of extrahepatic-growing type hepatic tumor: report of a case.

We herein report a 69-year-old woman who presented with a huge intra-abdominal tumor which demonstrated imaging findings similar to those of extrahepatic-growing type hepatic tumor, but turned out to be primary peritoneal papillary adenocarcinoma. Computed tomography showed a well-demarcated mass, measuring 12.0 cm in diameter, which came in contact with the lateral segment of the liver and invaded the diaphragm and abdominal wall. Distant lymph node metastasis was also detected. A fine-needle aspiration biopsy of the tumor showed poorly differentiated adenocarcinoma of unknown origin. After chemotherapy with 5-fluorouracil and cisplatin, the maximal diameter of the tumor decreased to 6.0 cm. The patient then underwent a tumorectomy together with a lateral segmentectomy of the liver, a splenectomy, a partial resection of the diaphragm and abdominal wall, and a left oophorectomy. Histological and immunohistochemical examinations demonstrated the tumor to be primary peritoneal papillary adenocarcinoma.

Decreased expression of CD28 coincides with the down-modulation of CD3zeta and augmentation of caspase-3 activity in T cells from hepatocellular carcinoma-bearing patients and hepatitis C virus-infected patients.

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection causes chronic inflammation and increases the risk of hepatocellular carcinoma (HCC). This immunosuppressive state may be one reason why HCV-infected patients often have multicentric cancers. Therefore, the purpose of the present study was to assess the cellular immune function in HCC-bearing and HCV-infected patients. METHODS: The expression of cluster of differentiation (CD)3zeta, CD28 and caspase-3 activity of peripheral blood T lymphocytes (PBL) from HCC-bearing patients, HCV-infected patients and normal subjects was measured by flow cytometric methods. Furthermore, intrahepatic T lymphocytes (IHL) and tumor-infiltrating T lymphocytes (TIL) from HCC patients were used. RESULTS: Decreased expressions of CD3zeta, CD28 and the augmentation of caspase-3 activity were recognized in PBL from HCC and HCV patients. These phenomena were more dominant in TIL and IHL than in PBL in HCC patients. Furthermore, the down-modulation of CD3zeta and increased caspase-3 activity occurred in CD28 down-modulated T cells. CONCLUSION: These results demonstrate impairment of the cellular immune system in HCC and HCV patients from the viewpoints of the down-modulation of CD3zeta and CD28 on T cells and T-cell apoptosis. In addition, the results imply that the down-modulation of CD3zeta and T-cell apoptosis take place in activated T cells.

[Efficacy of hepatic arterial infusion of adriamycin and mitomycin C mixed with degradable starch microspheres for liver metastasis of colorectal cancer--correlation with the mRNA expression of DNA topoisomerase-IIalpha and glutathione-S transferase-pi in primary lesions].

DNA topoisomerase-IIalpha (topo-IIalpha) is a target enzyme of adriamycin (ADM). Glutathione-S-transferase-pi is known to be correlated with the resistance of various anticancer drugs including mitomycin C (MMC) and ADM. Expression levels of topo-IIalpha and GST-pi mRNA of primary colorectal lesions were semi-quantitatively determined by the RT-PCR method in 22 patients with colorectal cancer, who underwent hepatic arterial infusion of ADM and MMC mixed with degradable starch microspheres for synchronous (n=17) or metachronous (n=5) liver metastasis. Expression of topo-IIalpha mRNA/beta-actin mRNA was 0.872+/-0.564 (mean+/-SD) in responders (PR, n=10) and 0.369+/-0.133 in non-responders (SD+PD, n=12) (p=0.047). The relative expression of GST-pi was 0.638+/-0.593 in responders and 1.014+/-0.682 in non-responders (p=0.22). These results suggest that determining the mRNA expression of topo-IIalpha is useful for predicting the efficacy for this regimen, whereas determining the mRNA expression of GST-pi is not.