Clinical efficacy of dual-phase scanning using (68)Ga-DOTATOC-PET/CT in the detection of neuroendocrine tumours.

AIM: To investigate whether delayed scanning at approximately 90 minutes post-injection of (68)Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide (DOTATOC) had any clinical benefits regarding the evaluation of neuroendocrine tumours (NETs), relative to conventional combined positron-emission tomography (PET) and computed tomography (CT) at 60 minutes post-injection. MATERIALS AND METHODS: Fifty-four patients who underwent DOTATOC-PET/CT for suspected or known NETs were retrospectively reviewed. PET/CT was performed twice at approximately 60 and 90 minutes post-injection. For visual analysis, a five-point grading scale (0: definitely normal to 4: definitely abnormal) was used, and grade 3-4 lesions were regarded as positive. For quantitative analysis, the time course of the maximum standardised uptake value (SUVmax) in each lesion and the mean SUV of physiological uptake in the liver were evaluated. RESULTS: Of the 54 patients, 43 had a total of 132 lesions. In interpreting the early images, there were four grade 3 lesions, and the remaining 128 lesions were grade 4. All 132 lesions were grade 4 in the delayed images. SUVs and tumour-to-liver ratios for hepatic lesions were slightly higher in delayed scanning than in early scanning (SUV, 26.8±21.2 versus 28.2±21.2 [p<0.01]; tumour-to-liver ratio, 5.9±4.5 versus 6.2±4.6 [p<0.01]), which did not affect the detection rate. Additionally, bone and peritoneal metastases had slightly higher SUVs at delayed imaging (p<0.05), but there was no difference in diagnostic performance. No significant difference in the SUVs for pancreatic lesions and primary sites in the bowel were observed between the early and delayed scans. CONCLUSION: Delayed scanning may be helpful for improving diagnostic confidence in some cases, although it provided no specific merits for diagnostic accuracy in detecting primary or metastatic NETs.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial).

BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV: NCT00660894.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Utility of FDG PET/CT in IgG4-related systemic disease.

IgG4-related systemic disease (IgG4-RSD) is an emerging clinical entity about which much remains to be elucidated, in terms of its aetiology, pathogenesis, diagnosis, treatment and outcome. Autoimmune pancreatitis (AIP) and Mikulicz disease (MD) are the two major, well-studied constituents of IgG4-RSD. AIP and MD have common characteristics of forming tumour-mimicking lesions that consist of lymphoplasmacytic infiltrates and fibrosclerosis with numerous immunoglobulin G4 (IgG4)-positive plasma cells, as well as various multi-organ manifestations of IgG4-RSD. 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/ computed tomography (FDG PET/CT) enables the acquisition of whole-body images and provides functional information about disease activity; as such it has a valuable role in staging extent of disease, guiding biopsy, and monitoring response to treatment. However, FDG PET/CT is likely to be only one component of the management strategy, and clinical, laboratory, imaging and histological findings are crucial in the overall diagnosis of the condition. At present FDG PET/CT does not have a well-established role in the assessment of patients with IgG4-RSD and future prospective studies are required to define the cost-effectiveness and clinical impact in this patient group more accurately.

Characteristics and outcome of suspected cerebrovascular disease in dogs: 66 cases (2009-2016).

OBJECTIVES: To characterise the clinical signs of suspected cerebrovascular disease in dogs. MATERIALS AND METHODS: Medical records of one hospital were searched from November 2009 to December 2016 for dogs that suffered of cerebrovascular disease. We diagnosed cerebrovascular disease based on acute onset, clinical signs and magnetic resonance imaging findings. The medical history, clinical signs, concurrent disease, area of infarction, cerebrospinal fluid results, month at onset and outcome were investigated in the cerebrovascular disease group and in a control group (dogs with brain disorders other than cerebrovascular disease). RESULTS: A total of 122 CVD cases were extracted from the 5312 patients that visited during the study period. Of these 122 cases, 66 (1.2%) matched the subject selection criteria of our study and were included in the analysis. Forebrain infarction was observed in 51 of 66 cases, of which 24 (47.1%) suffered from seizures. The number of dogs diagnosed with cerebrovascular disease was disproportionately high in August (nine of 59 cases) and December (13 of 59 cases). In the outcome survey, deterioration was observed in 11 of 55 cases. CLINICAL SIGNIFICANCE: Seizure is an important clinical sign of cerebrovascular disease in dogs. There was a significant seasonal variation in the number of dogs diagnosed with cerebrovascular disease in Japan. Clinical features observed in this report differ from those of previous reports and highlight the need for additional research in this area.

Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization.

Despite curative locoregional treatments for hepatocellular carcinoma (HCC), tumour recurrence rates remain high. The current study was designed to assess the safety and bioactivity of infusion of dendritic cells (DCs) stimulated with OK432, a streptococcus-derived anti-cancer immunotherapeutic agent, into tumour tissues following transcatheter hepatic arterial embolization (TAE) treatment in patients with HCC. DCs were derived from peripheral blood monocytes of patients with hepatitis C virus-related cirrhosis and HCC in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor and stimulated with 0·1 KE/ml OK432 for 2 days. Thirteen patients were administered with 5 × 106 of DCs through arterial catheter during the procedures of TAE treatment on day 7. The immunomodulatory effects and clinical responses were evaluated in comparison with a group of 22 historical controls treated with TAE but without DC transfer. OK432 stimulation of immature DCs promoted their maturation towards cells with activated phenotypes, high expression of a homing receptor, fairly well-preserved phagocytic capacity, greatly enhanced cytokine production and effective tumoricidal activity. Administration of OK432-stimulated DCs to patients was found to be feasible and safe. Kaplan-Meier analysis revealed prolonged recurrence-free survival of patients treated in this manner compared with the historical controls (P = 0·046, log-rank test). The bioactivity of the transferred DCs was reflected in higher serum concentrations of the cytokines IL-9, IL-15 and tumour necrosis factor-α and the chemokines CCL4 and CCL11. Collectively, this study suggests that a DC-based, active immunotherapeutic strategy in combination with locoregional treatments exerts beneficial anti-tumour effects against liver cancer.

Immune pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common complication of chronic hepatitis B virus (HBV) infection. The pathogenetic mechanisms potentially responsible for HCC during chronic HBV infection are not well defined. This study demonstrates that chronic immune-mediated liver cell injury triggers the development of HCC in the absence of viral transactivation, insertional mutagenesis, and genotoxic chemicals. These results strongly suggest that the immune response to HBV is both necessary and sufficient to cause liver cancer during chronic HBV infection, and that all other procarcinogenic events associated with HCC are probably dependent on this process.

Physiological uptake of 18F-fluorodeoxyglucose in uterine endometrium and myometrium: correlation with uterine motility evaluated by cine magnetic resonance imaging.

BACKGROUND: Accumulation of (18)F-fluorodeoxyglucose ((18)F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown. PURPOSE: To investigate the relationship between radiometabolic activity of (18)F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI). MATERIAL AND METHODS: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed. RESULTS: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32+/-1.47) than in those without contractions (2.45+/-0.66). CONCLUSION: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium.

Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.

Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system is a well-characterized tool for cancer gene therapy; however, it does not yet exhibit sufficient efficacy to cure patients of malignancies. We have reported that adenovirally delivered monocyte chemoattractant protein (MCP)-1 augmented the antitumor effects of the HSV-tk/GCV system in an athymic nude mouse model. The current study, which uses an immunocompetent mouse model of colon cancer, was designed to evaluate the antitumor effects of MCP-1 gene delivery in conjunction with this suicide gene therapy system. Subcutaneous tumor foci were directly transduced with both recombinant adenoviruses (rAds) expressing an HSV-tk gene and either of the MCP-1, CD80 and LacZ genes, followed by GCV administration. The growth of tumors was markedly suppressed by codelivery of HSV-tk and MCP-1 genes, which was exclusively associated with the recruitment of monocytes/macrophages, T helper 1 (Th1) cytokine gene expression and cytotoxic activity of the splenocytes. Furthermore, the antitumor effects were more efficient than that obtained by the combination of HSV-tk and CD80 genes. These results suggest an immunomodulatory effect of MCP-1 in the context of suicide gene therapy of colon cancer via orchestration of innate and acquired immune responses.

Analysis of the NPHP genes in two Japanese patients with suspected sporadic juvenile or adolescent nephronophthisis.

BACKGROUND: Mutations in 3 genes (NPHP1, NPHP3 and NPHP4) have been identified in patients with juvenile or adolescent nephronophthisis (NPHP) without extrarenal involvement, mainly in patients from western countries. In this study, we analyzed mutations in the NPHP genes of 2 Japanese patients with suspected sporadic juvenile or adolescent NPHP without extrarenal involvement. METHODS: A renal biopsy was performed in the 2 patients. Genomic DNA was prepared from peripheral blood mononuclear cells of the patients and their family members. The above NPHP genes were examined by deletion analysis or direct automated sequencing of polymerase chain reaction-amplified DNA products. RESULTS: Histological findings in the patients were compatible with those of NPHP. In 1 patient, we identified a novel deletion mutation including about half of exons of the NPHP1 gene. In another patient, there was no mutation in the NPHP genes examined. CONCLUSIONS: We found a novel NPHP1 deletion in 1 patient. To our knowledge, this is the second Japanese NPHP case in which genetic diagnosis was made.

Analysis of intrahepatic lymphocyte subsets in a transgenic mouse model of immune-mediated hepatocarcinogenesis.

Long-term, persistent liver cell injury increases the risk for hepatocellular carcinoma (HCC) development in chronic viral hepatitis. In support of this notion, we have developed a unique animal model of chronic immune-mediated liver disease that induces hepatocellular carcinogenesis using HBV transgenic mice; however, the intrahepatic inflammatory response was not precisely evaluated. The current study demonstrated that hepatitis B surface antigen (HBsAg)-specific cytotoxic T lymphocytes (CTLs) were detected at a frequency of 0.05% of CD8+ T lymphocytes in the liver, and that monocytes/macrophages were remarkably increased as the disease developed. These results suggest that a minimal number of intrahepatic virus-specific CTLs and the recruited monocytes/macrophages may contribute to the process of chronic liver inflammation.

Photocontrol of urease activity in spiropyran collagen membrane.

1. Collagen fibrils were modified with beta-1-[3,3-dimethyl-6'-nitrospiro-(indoline-2,2'-2H-benzopyran)] propionic anhydride. 2. Urease (urea amidohydrolase, EC 3.5.1.5) was immobilized in spiropyran collagen membrane. The activity of the urease-spiropyran collagen membrane was found to increase in the dark and then decrease with visible light irradiation. 3. The optimum pH of the urease-spiropyran collagen membrane under visible light was lowered in the dark. 4. The apparent Michaelis constant (K'm) of the urease-spiropyran collagen membrane in the dark was almost the same as that under visible light. The apparent maximum velocity was increased in the dark. 5. The diffusion coefficient of urea through the spiropyran collagen membrane in the dark was 1.4 times that under visible light. However, the increase of the diffusion rate was not responsible for the activity increase of the urease-spiropyran collagen membrane.

Photocontrol of urease-collagen membrane activity.

(1) Urease (EC 3.5.1.5.) was modified with beta-1-[3,3-dimethyl-6'-nitrospiro-(indoline-2,2'-2H-benzopyrene)] propionic anhydride. Three amino acid residues of urease were modified by the anhydride at a molar ratio of 2000. (2) The activity of modified urease was decreased with ultraviolet irradiation and then restored to the initial activity with visible light irradiation. (3) Modified urease was used to prepare a urease-collagen membrane. The apparent Michaelis constant (Km) of the modified urease-collagen membrane ultraviolet light was identical to that of the membrane under visible light. (4) The optimum pH of the modified urease-collagen membrane was displaced toward lower pH values with ultraviolet irradiation. At higher ionic strength, the pH activity curve of the membrane was displaced toward higher pH values. (5) The thermostability of urease was increased with its modification.

Onset and progression of diabetic glomerulosclerosis; a prospective study based on serial renal biopsies.

Clinical factors related to the development and progression of renal lesions were studied in twenty-three diabetics by the use of serial renal biopsies or autopsy. The results were as follows: Most of the juvenile and intermediate type diabetics were poorly controlled, with the glomerular lesion progressing rather rapidly. In contrast, many cases of the adult type were able to be maintained under good control and the renal lesion neither developed nor progressed. Two of the adult type diabetics with poor control showed slowly and slightly progressing renal lesions. The progression of glomerular lesions was significantly related to the control of blood glucose, type of diabetes, age at onset, type of treatment, and degree of obesity, but not to the duration of diabetes or the length of the follow-up period. There was a significant correlation between the type of diabetes and the control of blood glucose over the years. Arteriolar lesions developed concurrently with the progression of the glomerular lesion. Retinopathy also had a tendency to develop in proportion to the progress of glomerular lesions although it was not statistically significant. We have discussed the clinical factors responsible for the progression of diabetic glomerulosclerosis and have suggested that the type of diabetes rather than the degree of control of blood glucose might be more important in determining the development and progression of diabetic glomerulosclerosis. Nevertheless, the possibility remains that successful control of blood glucose may prevent or retard the development of diabetic glomerulosclerosis.

Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice.

To establish an effective nonviral gene delivery and a corresponding imaging method for i.p.-disseminated tumors, various oligonucleotide-carrier complexes were synthesized, and their in vitro and in vivo properties were examined. The 20-mer multiamino-linked oligonucleotide (oligo), synthesized as antisense against the c-erbB-2 sequence, and the 3'-biotinylated form of the same oligonucleotide (oligo-Bt) were (111)In labeled through a diethylenetriaminepentaacetic acid chelate. (111)In-oligo was mixed with generation 4 polyamidoamine dendrimer (G4) or with biotinylated G4 (G4-Bt), which are positively charged to form electrostatic complexes. (111)In-oligo/G4-Bt and (111)In-oligo-Bt were conjugated to avidin ((111)In-oligo/G4-Av and (111)In-oligo-Av, respectively). (111)In-oligo/G4, (111)In-oligo/G4-Av, (111)In-oligo-Av, and carrier-free (111)In-oligo (2.96 kBq/22.4-45.9 ng of oligo) were examined for internalization in vitro in human ovarian cancer cells (SHIN3). Biodistribution of (111)In-oligo-carrier complexes or (111)In-oligo was examined in normal (n = 4-7) or i.p. SHIN3 tumor-bearing (n = 6-10) mice 2-24 h after i.p. injection (74 kBq/125-300 ng). Scintigraphy of i.p. tumor-bearing and normal mice was performed at various times postinjection of (111)In-oligo-carrier complex or (111)In-oligo (1.85 MBq/2.2 ng). (111)In-oligo-carrier complexes bound to the tumor cells were internalized at a rate of 34-56% at 24 h. In vivo, G4, G4-Av, and Av significantly enhanced tumor delivery of (111)In-oligo [9.1, 14.5, and 24.4% of injected dose per g of tissue (ID/g) at 24 h; P < 0.05, < 0.01, and < 0.0001, respectively] compared with delivery without carrier (0.8% ID/g). Scintigrams of (111)In-oligo delivered to the i.p.-disseminated tumors by the carriers were successfully obtained. In conclusion, G4, G4-Av, and Av can effectively deliver (111)In-oligo to i.p.-disseminated tumors. (111)In-oligo-carrier complexes also have potential as tracers for imaging and monitoring of gene delivery.

Safety management of nuclear medicine personnel with visualisation of air dose rate.

Many people are anxious about radiation exposure for the reason that radiation cannot be seen. With the aim of devising a way for medical personnel to perform their medical duties without worry about radiation exposure, we attempted safety management using a system that displays the air dose of radiation in real time. Measurements were made in a lung ventilation scintigraphy examination room with the use of Xe-133. An SCI-type RI detector from Hamamatsu Photonics, which displays the air dose rate in real time, was used for the measurements. These radiation measurements were continued from the start to finish of the examination. The measurements were made in two locations, on the patient inhalation tube side and on the opposite side. Measurements were made on the patient tube side in 24 tests and on the opposite side in 12 tests. The maximum air dose rate was 3.7 ± 2.1 µSv/h on the patient tube side and 1.1 ± 0.5 µSv/h on the opposite side. Thus, the level on the opposite side was about 1/5 that of the tube side. To accurately perform lung ventilation scintigraphy, a medical worker needs to observe the patient's breathing status up close. Because of this, some medical workers are worried about radiation exposure during tests. The simplest way to reduce exposure would be to maintain a distance from the examination tube that is the source of radiation. The measurements in this study were made to encourage medical workers' recognition of this fact. Displaying specific numbers not only serves as basic data for managing staff operations, but is also thought to reassure workers through visualization.

Enhanced anti-tumor effects of herpes simplex virus thymidine kinase/ganciclovir system by codelivering monocyte chemoattractant protein-1 in hepatocellular carcinoma.

The therapeutic efficacy of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system in many types of tumors is unsatisfactory due to the insufficient spread of gene transfer and insufficient cell killing. In the current study, we investigated whether adenovirally delivered monocyte chemoattractant protein (MCP)-1 potentiates the antitumor effects of the HSV-tk/GCV system in hepatocellular carcinoma (HCC) cells. Subcutaneous tumor foci of the human HCC cell line, HuH7, established in athymic mice were directly transduced with a recombinant adenovirus (rAd) harboring an HSV-tk gene driven by a human alpha-fetoprotein promoter, followed by GCV administration. Subsequently, another rAd expressing MCP-1 under the universal CAG promoter was injected. The growth of tumors was markedly suppressed by codelivering HSV-tk and MCP-1 genes compared to that by either HSV-tk/GCV or MCP-1 delivery. In the tumor tissues, monocyte/macrophage infiltration was detected immunohistochemically. The antitumor effects of the rAd expressing MCP-1 were markedly reduced by the administration of carrageenan, a compound known to inactivate macrophage. These results indicate that adenovirally delivered MCP-1 enhanced the antitumor effects of the HSV-tk/GCV system synergistically by recruitment/activation of macrophages in tumor tissues, suggesting an effective immunotherapy for HCC and other lineages of tumors when used adjuvantly with a suicide gene.

Radioimmunotherapy of human glioma xenografts in nude mice by indium-111 labelled internalising monoclonal antibody.

The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.

Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.

To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.

Enhanced blood pressure response to regular daily stress in urban hypertensive men.

Twenty-eight urban untreated hypertensive men (mean age: 54 years; systolic (SBP)/diastolic (DBP) blood pressure at clinic: 148/96 mmHg] and 26 age- and sex-matched normal controls (54 years, 118/78 mmHg) were examined during normal daily activities by ambulatory blood pressure monitoring. When compared with home blood pressures, clinic blood pressures were 8/10% (SBP/DBP) higher in the hypertensives, but 1/3% lower in the normotensives. The values were significantly different for both groups (P less than 0.01 for SBP; P less than 0.001 for DBP). In contrast, the blood pressures fell in a similar manner in both groups during sleep. On working days, the blood pressures during work were 10/9% higher than the corresponding home blood pressures in the hypertensives and only 3/3% higher in the normotensives. These differences were significant (P less than 0.01 for both SBP and DBP). The results show that the blood pressures of hypertensives were hyperreactive to casual daily stress. In the normotensives, left ventricular wall thickness determined by echocardiography was correlated significantly with the blood pressures during work (r = 0.5, P less than 0.05 for SBP and DBP) and at home (r = 0.4, P less than 0.05 for SBP).