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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus.

There is substantial evidence that Kaposi sarcoma-associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1% O(2)) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS.

B-Lymphocytes↗
PubMed2001

Characterization of the bi-directional transcriptional control region between the human UFD1L and CDC45L genes.

The human UFD1L and CDC45L genes, adjacently located in the head-to-head direction on chromosome 22q11, are separated by a 884 base-pair (bp) segment constituting the putative transcriptional control region. In this region we mapped one transcription start site at 69 bp upstream of UFD1L gene, and one major and one minor start sites at 76 bp and 503 bp upstream of CDC45L gene, which are to center in the putative core promoters designated as P(UFD1L), P(CDC45L/major), and P(CDC45L/minor), respectively. The three core promoters lacked a TATA-motif and had a high GC-content. To determine the approximate ranges for the regulatory promoters, the 884-bp fragment or those with a series of deletions were placed between firefly and renilla luciferase genes present in the head-to-head direction in a single plasmid, and the resulting plasmids were assayed for the two transiently induced enzyme activities. The P(UFD1L) and P(CDC45L/major) regulatory promoters were within 418 and 454 bp upstream of the respective start sites and their greater parts were not overlapping. The activity of P(CDC45L/minor) regulatory promoter was markedly enhanced when P(CDC45L/major) and its regulatory promoter were deleted. The deletion analyses revealed the basal activities of the three core promoters, which were enhanced by approximately twofold by the respective regulatory promoters, on the transfected DNA templates.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Forced oral opening for cadavers with rigor mortis: two approaches for the myotomy on the temporal muscles.

Forensic dentistry plays an essential role in personal identification procedures. An adequate interincisal space of cadavers with rigor mortis is required to obtain detailed dental findings. We have developed intraoral and two directional approaches, for myotomy of the temporal muscles. The intraoral approach, in which the temporalis was dissected with scissors inserted via an intraoral incision, was adopted for elderly cadavers, females and emaciated or exhausted bodies, and had a merit of no incision on the face. The two directional approach, in which myotomy was performed with thread-wire saw from behind and with scissors via the intraoral incision, was designed for male muscular youths. Both approaches were effective to obtain a desired degree of an interincisal opening without facial damage.

Adult↗
PubMed2001

Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders.

Expression of a viral interleukin-6 (vIL-6) has been detected in certain Kaposi sarcoma (KS)--associated herpesvirus positive (KSHV(+)) lesions. The release of vIL-6 systemically and its contribution to the pathogenesis of HIV-related malignancies was studied. Serum vIL-6 was detected in 13 (38.2%) of 34 HIV(+) patients with KS, in 6 (85.7%) of 7 HIV(+) patients with primary effusion lymphoma (PEL) and/or multicentric Castleman disease (MCD), and in 18 (60.0%) of 30 HIV(+), mostly homosexual, individuals without KS, MCD, or PEL. By contrast, serum vIL-6 was detected in only 3 (23.1%) of 13 patients with classic KS, 1 (2.5%) of 40 blood donors from the United States, and 4 (19.0%) of 21 blood donors from Italy. Circulating vIL-6 levels were associated with HIV(+) status (P <.0001). However, within the HIV(+) cohort, serum vIL-6 levels were not associated with the occurrence of KSHV-associated malignancies (P =.43). (Blood. 2001;97:2173-2176)

Anti-HIV Agents↗
PubMed2001

Initiation of polyoma virus origin-dependent DNA replication through STAT5 activation by human granulocyte-macrophage colony-stimulating factor.

Several lines of evidence indicate that transcriptional activation is coupled with DNA replication initiation, but the nature of initiation of DNA replication in mammalian cells is unclear. Polyoma virus replicon is an excellent system to analyze the initiation of DNA replication in murine cells because its replication requires an enhancer, and all components of replication machinery, except for DNA helicase large T antigen, are supplied by host cells. This system was used to examine the role of signal transducer and activator of transcription (STAT5) in replication initiation of polyoma replicon in the mouse lymphoid cell line BA/F3. The plasmid with tandem repeats of consensus STAT5 binding sites followed by polyoma replication origin was replicated by stimulation with human granulocyte-macrophage colony-stimulating factor (hGM-CSF) in the presence of polyoma large T antigen in BA/F3 cells. Mutation analysis of the hGM-CSF receptor beta subunit revealed that only the box1 region is essential, and the C-terminal tyrosine residues are dispensable for the activity. Addition of the tyrosine kinase inhibitor genistein suppressed this replication without affecting transcriptional activation of STAT5. Because deletion analysis of STAT5 indicates the importance of the C-terminal transcriptional activation domain of STAT5 for the initiation of replication, the role of this region in the activation of replication was examined with a GAL4-STAT5 fusion protein. GAL4-STAT5 activated replication of the plasmid containing tandem repeats of GAL4 binding sites and polyoma replication origin in BA/F3 cells. Mutation analysis of GAL4-STAT5 indicated that multiple serine residues coordinately have a role in activating replication. This is the first direct evidence indicating the potential involvement of STAT5 in replication.

Animals↗
PubMed2001

Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. I. Effect on the cerebral infarction and edema at the acute stage of permanent middle cerebral artery occlusion in rats.

The effect of a novel Na+/Ca2+ channel blocker NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] on the cerebral infarction, edema and brain energy metabolism was investigated in rats after permanent middle cerebral artery occlusion (MCAO). The infarction and brain water content were evaluated at 48 h and 24 h after MCAO, respectively. A single bolus injection of NS-7 (0.03125-0.25 mg/kg) immediately after MCAO produced a dose-dependent reduction in the infarct volume as well as edema both in the cerebral cortex and striatum. Glycerol (4 g/kg) also decreased water content both in the occluded and non-occluded brain, but it did not reduce the size of cerebral infarction. Unlike glycerol, NS-7 did not change the water content in non-occluded brain. Moreover, a significant protective action was still observed even when NS-7 was injected once at 12 h after occlusion. In addition, NS-7 significantly reversed the decrease in tissue ATP content observed at 3 h but not at 0.5 h after MCAO. These findings suggest that a Na+/Ca2+ channel blocker NS-7 protects cerebral tissues against ischemic insults by improving the disturbance of cerebral energy metabolism and suppressing the cerebral edema.

Adenosine Diphosphate↗
PubMed2001

Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. II. Effect on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of permanent middle cerebral artery occlusion in rats.

We have previously shown that NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] reduces the size of cerebral infarction measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h after permanent middle cerebral artery occlusion (MCAO) in rats. To determine whether NS-7 improves the pathological and behavioral changes at the chronic stage of MCAO, the effect of this compound on the cerebral infarction as well as the neurological and cognitive impairments was investigated 7 days after MCAO. Single or five daily injections of NS-7 (0.125-0.5 mg/kg, i.v.) significantly reduced the infarct volume and improved the neuronal dysfunction including the hind leg paralysis, walking disability and motor incoordination, and the deficit of passive avoidance task, although the neuroprotective efficacy was not different among these dosing regimens. On the other hand, the effects of single versus repeated injections of NS-7 at 0.1 or 0.2 mg/kg on the neurological symptoms were compared at 4 weeks after MCAO. At a lower dose, repeated but not single injection of NS-7 significantly improved the neurological symptoms, although the single injection was effective at a higher dose. From these findings, it is suggested that NS-7 reverses the behavioral and cognitive dysfunction observed at the chronic stage of cerebral ischemia by suppressing the cerebral infarction.

Animals↗
PubMed2001

Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferon: A meta-analysis of randomized trials.

CONTEXT: Hepatitis C is the leading cause of chronic liver disease in the United States. Several trials have found that interferon and ribavirin combination therapy is more efficacious than interferon monotherapy for previously untreated patients and those who relapsed after prior interferon monotherapy, but its effectiveness for nonresponders to prior interferon monotherapy is unclear. OBJECTIVE: To assess the efficacy and safety of interferon and ribavirin vs interferon alone for treatment of patients with chronic hepatitis C who previously did not respond to interferon monotherapy. DATA SOURCES: A systematic search was performed using MEDLINE and the Science Citation Index for publications from 1966 to December 1999. A manual reference search and a manual review of relevant specialty journals also were performed, and input from clinical hepatology experts was sought. STUDY SELECTION: Included studies were randomized, controlled clinical trials comparing interferon and ribavirin with interferon alone and reporting virological and biochemical outcomes after a follow-up period. Of 50 identified studies, 12 trials (941 patients) were included in the analysis. DATA EXTRACTION: Two investigators reviewed trials independently for methods, inclusion and exclusion criteria, and outcomes. Disagreements were resolved by discussion. Abstracted data included study and patient characteristics and virological, biochemical, and histological outcomes. A quality evaluation questionnaire was used to score studies. DATA SYNTHESIS: The pooled virological response rate for combination therapy was 14% (95% confidence interval [CI], 11%-17%), with a risk difference favoring combination therapy of 7% (95% CI, 2%-13%). Use of interferon alfa-2a/2b and ribavirin, 1000 to 1200 mg/d, was associated with a pooled virological response rate of 18% and a risk difference of 16% (95% CI, 11%-21%). When interferon alfa-n/n3 and a lower dosage of ribavirin (600-800 mg/d) were used, the risk difference was 0% (95% CI, -7% to 7%). Combination therapy was associated with more adverse effects and an increased rate of discontinuation of treatment compared with interferon monotherapy. CONCLUSIONS: For chronic hepatitis C that is nonresponsive to prior interferon monotherapy, combination therapy is more effective than re-treatment with interferon alone. Response rates remain less than 20% even in the most responsive subgroups, demonstrating a need for better therapeutic options.

Antiviral Agents↗
PubMed2001

Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans as endocrine disrupters--what we have learned from Yusho disease.

Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans (PCDFs) are persistent environmental pollutants. In some areas wildlife reproduction has been affected by these compounds, which are recognized as endocrine disrupters. In 1968 in northern Kyushu in Japan about 2000 people were poisoned by PCBs and PCDFs (pyrolysis products of PCBs) which contaminated rice oil. Their condition was named "Yusho" disease. A similar poisoning by PCBs in Taiwan was named "Yu-Cheng" disease. The major symptoms of Yusho disease were dermal and ocular lesions, but some of the symptoms, such as irregular menstrual cycles and altered immune responses, were notable with respect to the endocrine disrupting activities of PCBs and related compounds. Several important observations relevant to the mechanisms of Yusho have been made from animal studies. For example, a coplanar PCB congener was shown to cause atrophy of the thymus and PCB administration was thought to alter androgen metabolism. The most tragic aspect of Yusho and Yu-Cheng diseases was the exposure of children to PCBs. In the case of Yu-Cheng, children exposed to PCBs in utero and lactationally were reported to have poor cognitive development. Intellectual impairment was also observed in children born to women who had eaten fish contaminated with PCBs in the United States. From animal studies, alterations in thyroid hormone status, modulation of protein kinase C, and changes in dopamine levels, etc. were proposed as the possible mechanisms for the adverse effects of PCBs on brain development. Whereas coplanar PCB and related congeners, e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin, induce gene expression via a ligand-dependent transactivating factor, the arylhydrocarbon receptor, alternative pathways for gene expression, e.g., c-Src and cross talk with the MAP kinase pathway, are also reviewed with respect to understanding the toxic mechanisms of these compounds. Finally, the "precautionary principle" is discussed for prevention of the health hazards caused by exposure to endocrine disrupters.

Animals↗
PubMed2001

Neoadjuvant chemotherapy using low-dose consecutive intraarterial infusions of cisplatin combined with 5-fluorouracil for locally advanced cervical adenocarcinoma.

OBJECTIVE: The goal of this work was to evaluate response rate, toxicity, and survival in treatment with intraarterial 5-fluorouracil (5-FU) and cisplatin in a neoadjuvant setting; this combination was administered to patients with locally advanced cervical adenocarcinoma. METHODS: Eleven patients were treated with preoperative neoadjuvant chemotherapy. Those eligible included patients with previously untreated stage IB, II, or III adenocarcinoma with good performance status. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (a total of 10 mg/day) for 30 min, followed by 5-FU (a total of 250 mg/day) given by 24-hour continuous infusion for 10 days. Treatment was repeated every 3 weeks for a total of two or three cycles. All except one patient with progressive disease underwent radical hysterectomy following neoadjuvant chemotherapy. Postoperative radiotherapy was given to the whole pelvis to 6 patients; 3 of the 6 patients with involved common iliac nodes received radiotherapy to a paraaortic field in addition to the whole pelvis. RESULTS: Among 11 eligible patients, 7 had a partial response (64%). Stable disease was observed in 3 cases (27%) and progressive disease in 1 (9%). Histopathological changes related to chemotherapy, however, revealed only mild effects. Of the 24 treatment cycles administered, no Grade 3 or 4 toxicity was observed and there were no therapy-related deaths. The median follow-up period was 30 months (range, 1-65 months). The mean survival period was 34.7 months and the 5-year survival rate was 21.2%. CONCLUSIONS: Intraarterial neoadjuvant chemotherapy effectively reduced tumor size in patients with locally advanced cervical adenocarcinoma; however, a survival advantage was not clear.

Adenocarcinoma↗
PubMed2001

Stage III endometrial cancer: analysis of prognostic factors and failure patterns after adjuvant chemotherapy.

OBJECTIVE: This study was performed to assess the prognostic factors and patterns of recurrence in stage III endometrial carcinoma treated with surgery and adjuvant chemotherapy. METHODS: A retrospective review of 61 stage III endometrial carcinoma patients treated between 1988 and 1998 at Niigata University Hospital was performed. All patients underwent surgery, followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. RESULTS: The 5-year disease-free survival was 78.6%. Multivariate analysis revealed deep myometrial invasion and lymph-vascular space involvement correlated significantly with disease-free survival. Based on these two factors, the patients could be divided into low-risk and high-risk groups. The 5-year disease-free survival for the low-risk group was 100%, which was significantly better than the 59.1% for the high-risk group. Disease recurrence occurred in 13 of 30 high-risk patients, and there was no recurrence in the 31 low-risk patients. Looking at the patterns of recurrence for the high-risk group by lymph node metastasis, 5 recurrences were locoregional, 1 was locoregional/distant, and 1 was distant in 16 node-positive high-risk patients. In 14 node-negative patients, 5 had distant and 1 had locoregional/distant recurrences. CONCLUSIONS: The locoregional failure in the node-positive high-risk group deserves further attention. For improvement of locoregional control, it may be worthwhile to consider new strategies. The role of new adjuvant chemotherapy should be investigated to control distant failure in node-negative high-risk patients.

Adult↗
PubMed2001

Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix.

OBJECTIVE: To evaluate the response rate and toxicity and to improve survival, neoadjuvant chemotherapy (NAC) was utilized in patients younger than 50 years with locally advanced cervical squamous cell carcinoma. METHODS: Twenty-one patients were treated with preoperative NAC. Eligibility included patients with previously untreated stage IB or IIA with deep stromal invasion assessed by magnetic resonance imaging or bulky tumor or IIB squamous cell carcinoma who were younger than 50 years. The NAC consisted of cisplatin (60 mg/m(2)) on day 1, vinblastine (4 mg/m(2)/day) on days 1 and 2, and peplomycin (10 mg/day) on days 1, 8, and 15 (PVP). Treatment was repeated every 3 weeks for a total of two cycles. All 21 patients underwent radical hysterectomy following NAC. Postoperative radiotherapy was given to 18 patients. We used 21 patients who underwent radical hysterectomy and postoperative radiation therapy as a nonrandomized control group. RESULTS: The response rate for NAC was 86% (18/21). Two patients required discontinuation of PVP treatment after one administration because of grade 4 neutropenia and thrombocytopenia, and decreased carbon monoxide diffusion capacity, respectively. In the NAC group, stromal invasion was significantly reduced (P = 0.0103), and the incidence of lymph node metastasis was decreased. No patients had positive parametrial and vaginal margins. The overall 5-year survival rate was 84.0% in the NAC group, which was significantly better than that in the control group (58.9%) (P = 0.0434). CONCLUSIONS: NAC for younger patients with locally advanced cervical carcinoma is thought to be safe, well tolerated, effective, and useful for increasing operability, decreasing pathological risk factors, and improving survival.

Adult↗
PubMed2001

Patent foramen ovale complicated by paradoxical embolism and brain infarct in a patient with advanced ovarian cancer.

BACKGROUND: Recent investigations of patients with cerebral and peripheral arterial emboli of unknown cause suggest that paradoxical embolism through a patent foramen ovale might be responsible for more arterial embolic events than previously realized. CASE: A 60-year-old woman with advanced ovarian cancer presented with sudden onset of expressive aphasia and right upper hemiplegia postoperatively. A patent foramen ovale diagnosed by echocardiography with contrast combined with the presence of thrombosis in her right femoral vein leads us to speculate that her stroke was secondary to a paradoxical embolism. CONCLUSION: Paradoxical embolism should be considered in the differential diagnosis of ovarian cancer patients with embolic stroke and it may be appropriate to include a cardiac echo as part of the diagnostic evaluation.

Brain Infarction↗
PubMed2001

Transient seizure activity demonstrated by Tc-99m HMPAO SPECT and diffusion-weighted MR imaging.

Cerebral perfusion single photon emission computed tomography (SPECT) has been used to confirm the localization of the epileptic focus and the evaluation of seizure. Recently, diffusion-weighted MR imaging (DWI) has been recognized for evaluation of seizure activity. We describe a case of transient seizure activity demonstrated by Tc-99m HMPAO SPECT and DWI. This patient was a 61-year-old woman with a 10-month history of right middle cerebral artery (MCA) infarction who had a generalized seizure during MRI. DWI immediately after seizure showed transient hyperintensity in the right frontal gray matter and the white matter, and these apparent diffusion coefficients (ADC) were transiently decreased. This transient hyperintensity on DWI corresponded to transient hyperperfusion identifying the epileptic focus on interictal Tc-99m HMPAO SPECT. Transient sustained seizure activity might cause these changes on DWI and SPECT. It was considered that interictal Tc-99m HMPAO SPECT showed the delayed hyperperfusion caused by excitatory neuronal overaction and DWI showed cytotoxic edema seizure-induced by energy failure of the membrane-bound Na/K-ATPase pump.

Cerebral Infarction↗
PubMed2001

Interictal crossed cerebellar hyperperfusion on Tc-99m ECD SPECT.

Crossed cerebellar hyperperfusion (CCH) in epilepsy is a rare condition that is observed on ictal cerebral perfusion SPECT. The mechanism of CCH assumes that hyperperfusion in the epileptic foci of the unilateral supratentorium causes hyperperfusion secondary to the corticopontocerebellar pathway (CPCP)-mediated remote effect in the contralateral cerebellar hemisphere. This phenomenon is similar to that of crossed cerebellar diaschisis (CCD). In this report we demonstrated interictal CCH in a patient with epilepsy in technetium-99m-ethyl cysteinate dimer (Tc-99m ECD) SPECT of the brain. To the best of our knowledge, interictal CCH has not been reported in the literature. This is the first report to describe the phenomenon with interictal Tc-99m ECD SPECT.

Aged↗
PubMed2001

Bilateral crossed cerebello-cerebral diaschisis and mutism after surgery for cerebellar medulloblastoma.

A 7-year-old boy developed mutism after surgery for cerebellar medulloblastoma. Postoperative magnetic resonance imaging (MRI) showed atrophy of the cerebellar vermis and both cerebellar hemispheres, predominantly on the right side. Single photon emission computed tomography (SPECT) with technetium-99m-ethyl cysteinate dimer (Tc-99m ECD) revealed decreased cerebral blood flow (CBF) in the bilateral thalami, bilateral medial frontal lobes, and left temporal lobe in addition to the cerebellar vermis and both cerebellar hemispheres when mutism was manifest, indicating the existence of bilateral crossed cerebello-cerebral diaschisis (BCCCD). Circulatory disturbance in both cerebellar hemispheres secondary to tumor resection probably caused BCCCD in both cerebral hemispheres, predominantly in the left, via the dentatothalamocortical pathway (DTCP). With recovery of his mutism, CBF increased in the right thalamus, bilateral medial frontal lobes and left temporal lobe. Thus BCCCD was improved, with only a slight decrease in CBF still persisting in the left thalamus. The mechanism of mutism may have involved damage to the cerebellar vermis (the site of incision at operation), the left dentate nucleus (heavily infiltrated by the tumor) and the right dentate nucleus of the cerebellum (affected by circulatory disturbance secondary to acute postoperative edema). The SPECT findings suggested that mutism was associated with BCCCD-induced cerebral circulatory and metabolic hypofunction in the supplementary motor area mediated via the DTCP.

Cerebellar Neoplasms↗
PubMed2001

Phase 1 clinical trial of irradiated autologous melanoma cells adenovirally transduced with human GM-CSF gene.

The objective of this study was to determine the safety and antitumor activity of an autologous GM-CSF-secreting melanoma cell vaccine that was engineered ex vivo with recombinant replication-incompetent adenovirus harboring a human GM-CSF gene (Adv/hGM-CSF). Melanoma samples were surgically obtained from 30 patients (15 female and 15 male, ages ranging from 23 to 87) and were processed for vaccine preparation. Due to stringent eligibility criteria, 9 out of 30 patients were enrolled in the phase 1 clinical trial (FDA IND7677). Melanoma cell lines established from surgical specimens of 9 patients were transduced with Adv/hGM-CSF (MOI of 100) and subsequently irradiated at 35 Gy. These cell lines secreted human GM-CSF in vitro at an average rate of 80-424 ng/10(6) cells/24 h. All patients were intradermally and subcutaneously injected at several sites with irradiated autologous melanoma cells (2x10(6)-1x10(7) in 300 microl saline), 2-10 times, at intervals of 4-8 weeks. None of the patients vaccinated showed any serious adverse systemic response. Three patients (nos.1, 6 and 7) demonstrated local reaction (erythema) to the vaccination. Tumor-specific CTL assays performed in the absence of K562 cells showed that the levels of CTLs in peripheral blood of 5 patients increased following vaccination, whereas those in one patient declined. Levels of CTLs assayed in the presence of K562 cells were considerably lower than those assayed in the absence of K562 cells, but were also found to increase following vaccination in the peripheral blood of 6 patients. A patient who had been vaccinated 10 times (patient 1) responded to the vaccination by apparent reduction in size of metastatic tumor in the lung. Immunohistochemical examination of the vaccination sites of patient 1, biopsied after the 3rd and 4th vaccination. showed that the vaccination sites responded with infiltration of inflammatory cells, such as T cells (CD3+, CD8+), macrophages and dendritic cells (CD83+), for a period up to about 8 days. These data suggest that repeated vaccinations with irradiated autologous GM-CSF-producing tumor cells were well tolerated by patients and led to the activation of an antitumor immune response in some patients.

Adenoviridae↗