ABSTRACT
A delayed presentation of traumatic spinal epidural hematoma (SEH) is a rare disease in which most patients are asymptomatic for days to weeks after the injury, followed by pain and then a neurological deficit. A 66-year-old woman who suffered a fractured right clavicle due to a bicycle accident 42 days previously, presented with left shoulder pain and left hemiplegia. The manual muscle test (MMT) scores of the left upper and lower limbs were all 1. Computed tomography and magnetic resonance imaging showed no cervical fracture but showed cervical epidural hematoma. She underwent surgery for the removal of the SEH. Her MMT score improved to 4 at 10 days after surgery. Even in cases with a delayed presentation, suspecting SEH can help clinicians make an early diagnosis. Additionally, the prompt surgical evacuation of the SEH can lead to favorable neurological outcomes in symptomatic cases.
ABSTRACT
Introduction: Blunt cervical injuries rarely cause vertebral artery injuries (VAIs), such as vertebral artery (VA) dissection or occlusion. To prevent subsequent embolic infarction, embolization of the injured VA is needed before surgical fixation of the cervical spine. However, evidence on endovascular treatment for asymptomatic low-grade VAIs with blunt traumatic cervical injury is insufficient. Case Report: In the present case, a 79-year-old Japanese man presented tetraparesis after falling while walking. Digital subtraction angiography showed no intimal flap and only slight stenosis of the right VA. Embolization was not performed before spinal decompression surgery for this low-grade injury. However, on the 3rd day after surgery, diffuse-weighted imaging showed dot-like high signal intensity in the right thalamus and right posterior lobe, and magnetic resonance angiography (MRA) showed near occlusion of the right VA. 8 days after surgery, MRA showed recanalization of the right VA flow. We performed VA embolization to prevent emboli scattering to the distal region during recanalization of the intracranial blood flow. Conclusion: According to the relevant literature, prophylactic embolization may be indicated to prevent the embolic infarction not only in cases of VA occlusion requiring fixation of the cervical spine but also in cases of low-grade VAIs in which fixation is not required. Embolization of the VA before spinal surgery might be an aggressive treatment strategy that avoids serious embolic infarction disorder after VAIs.
ABSTRACT
Breast cancer, a leading cause of death yearly, has been shown to be initiated and propagated by cancer stem cells. CD133, a cell surface antigen, has been shown to be present on cancer stem cells of many solid tumors, including breast cancer. A limitation to targeting CD133 is major histocompatibility complex (MHC)-restricted presentation of epitopes, leading to activation of only one arm of the immune system: either CD4+ helper T cells or CD8+ cytotoxic T cells. Thus, we hypothesized that by creating an MHC-independent vaccination, we would give rise to a sustained immune response against CD133 in triple-negative breast cancer (TNBCs). We transfected CD133 mRNA into dendritic cells and then tested this in animal models of TNBC. We showed in these models the activation of both CD8+ cytotoxic T cells and CD4+ helper T cells by dendritic cell vaccination with modified CD133 mRNA, with subsequent decrease in tumor growth. This study for the first time demonstrates in a syngeneic mouse model of TNBC that targeting CD133, in an MHC-independent manner, is an effective strategy against the cancer stem cell population, leading to tumor abrogation.
ABSTRACT
Cancer stem cells are initiating cells of cancer and propagate its growth through self-renewal and differentiation of its daughter cells. CD133 is a cell surface antigen that is present on glioma stem cells and has been used to prospectively isolate glioma stem cells. We hypothesized that a major histocompatibility complex (MHC)-independent and long-lasting immune response against CD133 could be generated by transfecting CD133 mRNA into dendritic cells and vaccinating animals with experimental gliomas. To test this hypothesis, we developed a novel humanized mouse model using CD34-positive hematopoietic stem cells. We confirmed the robust simultaneous activation of CD8- and CD4-positive T cells by dendritic cell vaccination with modified CD133 mRNA leading to a potent and long-lived immune response, with subsequent abrogation of CD133-positive glioma stem cell propagation and tumor growth. This study for the first time demonstrates in both a humanized mouse model and in a syngeneic mouse model of glioblastoma that targeting a glioma stem cell-associated antigen is an effective strategy to target and kill glioma stem cells. This novel and simple humanized mouse model for immunotherapy is a significant advance in our ability to test human-specific immunotherapies for glioblastoma.
ABSTRACT
Helicoverpa armigera (Hübner) is a notorious agricultural pest native to the Old World. Recently, its invasion into South and Central America has become a serious problem in the New World. The rapid detection of invasive pests is essential to eradicate them and prevent establishment. However, an extremely similar species, H. zea (Boddie) distributed in the New World makes identification difficult. Helicoverpa armigera and H. zea have only minor differences in male genitalia to separate them morphologically. Both species are attracted to the same pheromone lure, and it takes considerable time and effort to identify them from bulk samples obtained during trap monitoring. Although several molecular approaches based on PCR have been reported, these methods require expensive equipment and are unsuitable for onsite diagnostics. Here, we developed a rapid and convenient diagnostic method based on the loop-mediated isothermal amplification to distinguish H. armigera from related species: H. zea, H. assulta (Guenée), H. punctigera (Wallengren), and Chloridea virescens (Fabricius). The diagnostic method makes it possible to detect H. armigera within 90 min only using simple equipment. The method also worked with mixed DNA templates containing excess DNA from H. zea at the ratio of 1:999 (H. armigera:H. zea). This method can be an effective tool for onsite diagnostics during monitoring surveys for invasive H. armigera.
Subject(s)
Insect Control/methods , Moths/classification , Nucleic Acid Amplification Techniques/methods , Animals , Moths/geneticsABSTRACT
Dantrolene is used for malignant hyperthermia during anesthesia, and it sometimes causes severe liver injury as a side effect. Dantrolene is metabolized to acetylaminodantrolene, which is formed via the reduction of dantrolene to aminodantrolene and subsequent acetylation. Formation of hydroxylamine during the metabolic process may be associated with liver injury. We identified the enzymes responsible for dantrolene metabolism in humans to elucidate the mechanism of liver injury. Dantrolene reductase activity was not detected in human liver microsomes, but it was detected in cytosol. Formation was increased in the presence of N1-methylnicotineamide, which is an electron donor to aldehyde oxidase 1 (AOX1). Potent inhibitors of AOX1 and a correlation study with a marker of AOX1 activity, namely phthalazine oxidase activity, in a panel of 28 human liver cytosol samples supported the role of AOX1 in dantrolene reduction. Acetylaminodantrolene formation from aminodantrolene was highly detected in recombinant N-acetyltransferase (NAT) 2 rather than NAT1. A glutathione trapping assay revealed the formation of hydroxylamine via an AOX1-dependent reduction of dantrolene but not via hydroxylation of aminodantrolene. In conclusion, we found that AOX1 and NAT2 were responsible for dantrolene metabolism in humans and that AOX1-dependent metabolism determines dantrolene-induced liver injury.
Subject(s)
Aldehyde Oxidase/metabolism , Arylamine N-Acetyltransferase/metabolism , Chemical and Drug Induced Liver Injury/enzymology , Dantrolene/metabolism , Liver/enzymology , Neuromuscular Agents/metabolism , Chemical and Drug Induced Liver Injury/etiology , Cytosol/drug effects , Cytosol/enzymology , Dantrolene/adverse effects , Female , Humans , Liver/drug effects , Male , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Neuromuscular Agents/adverse effectsABSTRACT
To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4) esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive preoperative treatment and underwent three-field lymph node dissection in the Juntendo University Hospital between December, 2004 and December, 2009. The tumors were histologically diagnossed as squamous cell carcinoma. The patients were divided into two groups, a surgery alone group (S group, 88 patients) and a group that received postoperative DCF therapy (DCF group, 51 patients). The disease-free and overall survival were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as N1 and N2, according to the TNM classification. There were no significant differences between the S and DCF groups regarding clinicopathological factors other than intramural metastasis and main tumor location. The presence of intramural metastasis, blood vessel invasion and the number of lymph nodes were identified as prognostic factors. The 5-year disease-free and overall survival were 55.8 and 57.3%, respectively, in the S group and 52.8 and 63.0%, respectively, in the DCF group. These differences were not considered to be statistically significant (P=0.789 and 0.479 for disease-free and overall survival, respectively). Although there were no significant differences in disease-free and overall survival between the S and DCF groups in N1 cases, both disease-free and overall survival were found to be better in the DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%, respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF was shown to improve disease-free and overall survival in moderate lymph node metastasis-positive cases (N2), suggesting that the DCF regimen may be effective as postoperative adjuvant chemotherapy for patients with lymph node metastasis from esophageal cancer.
ABSTRACT
Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The novel nanoprodrug contains a derivative of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen in an emulsion with the antioxidant α-tocopherol. The ibuprofen derivative, Ibu2TEG, contains a tetra ethylene glycol (TEG) spacer consisting of biodegradable ester bonds. The biodegradable ester bonds ensure that the prodrug molecules break down hydrolytically or enzymatically. The drug is labeled with the fluorescent reporter Cy5.5 using nonbiodegradable bonds to 1-octadecanethiol, allowing us to reliably track its accumulation in the brain after TBI. We delivered a moderate injury using a highly reproducible mouse model of closed-skull controlled cortical impact to the parietal region of the cortex, followed by an injection of the nanoprodrug at a dose of 0.2 mg per mouse. The blood brain barrier is known to exhibit increased permeability at the site of injury. We tested for accumulation of the fluorescent drug particles at the site of injury using confocal and bioluminescence imaging of whole brains and brain slices 36 hours after administration. We demonstrated that the drug does accumulate preferentially in the region of injured tissue, likely due to an enhanced permeability and retention (EPR) phenomenon. The use of a nanoprodrug approach to deliver therapeutics in TBI represents a promising potential therapeutic modality.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Brain Injuries/metabolism , Ibuprofen/administration & dosage , Prodrugs , Reactive Oxygen Species/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Antioxidants/chemistry , Behavior, Animal , Brain Injuries/drug therapy , Brain Injuries/pathology , Disease Models, Animal , Functional Neuroimaging , Ibuprofen/chemistry , Ibuprofen/metabolism , Luminescent Measurements , Male , Maze Learning , Mice , Prodrugs/administration & dosage , Prodrugs/chemistry , alpha-Tocopherol/chemistryABSTRACT
Chemotherapy for intracranial gliomas is hampered by limited delivery of therapeutic agents through the blood brain barrier (BBB). An optimal therapeutic agent for brain tumors would selectively cross the BBB, accumulates in the tumor tissue and be activated from an innocuous prodrug within the tumor. Here we show brain tumor-targeted delivery and therapeutic efficacy of a nanometer-sized prodrug (nanoprodrug) of camptothecin (CPT) to treat experimental glioblastoma multiforme (GBM). The CPT nanoprodrug was prepared using spontaneous nanoemulsification of a biodegradable, antioxidant CPT prodrug and α-tocopherol. The oxidized nanoprodrug was activated more efficiently than nonoxidized nanoprodrug, suggesting enhanced therapeutic efficacy in the oxidative tumor microenvironment. The in vitro imaging of U-87 MG glioma cells revealed an efficient intracellular uptake of the nanoprodrug via direct cell membrane penetration rather than via endocytosis. The in vivo study in mice demonstrated that the CPT nanoprodrug passed through the BBB and specifically accumulated in brain tumor tissue, but not in healthy brain tissue and other organs. The accumulation preferably occurred at the periphery of the tumor where cancer cells are most actively proliferating, suggesting optimal therapeutic efficacy of the nanoprodrug. The nanoprodrug was effective in treating subcutaneous and intracranial tumors. The nanoprodrug inhibited subcutaneous tumor growth more than 80% compared with control. The median survival time of mice implanted with an intracranial tumor increased from 40.5 days for control to 72.5 days for CPT nanoprodrug. This nanoprodrug approach is a versatile method for developing therapeutic nanoparticles enabling tumor-specific targeting and treatment. The nontoxic, tumor-specific targeting properties of the nanoprodrug system make it a safe, low cost, and versatile nanocarrier for pharmaceuticals, imaging agents, and diagnostic agents.
Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Camptothecin/administration & dosage , Glioblastoma/drug therapy , Glioblastoma/metabolism , Nanocapsules/administration & dosage , Prodrugs/administration & dosage , Reactive Oxygen Species/metabolism , Animals , Antioxidants/administration & dosage , Brain Neoplasms/pathology , Camptothecin/chemistry , Cell Line, Tumor , Glioblastoma/pathology , Mice , Nanocapsules/chemistry , Nanocapsules/ultrastructure , Treatment Outcome , alpha-Tocopherol/administration & dosageABSTRACT
Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. Up to 2011, approximately 300 cases had been reported worldwide. The average age of onset is 60.5 years old, with a prevalence of males (2:1). A typical finding of PMME is a lobular or polyploid, well-circumscribed and pigmented tumor, partly covered with normal mucosa. PMME represents various colors depending on its melanin quantity and commonly coexists with intramural metastases, melanocytosis or melanoma in situ. The tumor is located from the middle to lower thoracic esophagus. The accuracy of diagnosis from biopsy is approximately 80%, because many cases are misdiagnosed as a poorly differentiated carcinoma because of the absence of melanin granules. A definite diagnosis was made by immunohistochemical examination with positive results of S100 protein, HMB45 and neuron-specific enolase. PMME has a highly metastatic potential, and the incidence of distant metastasis at the initial diagnosis is around 40-80%. A metastatic tumor from cutaneous malignant melanoma is another pigmented esophageal tumor to be considered when making the differential diagnosis for PMME. Junctional activity with melanotic cells in the adjacent epithelium and the presence of in situ melanoma and/or a satellite tumor without a previous history of cutaneous melanoma are definitive. Most of the reported patients were treated with radical esophagectomy, which is believed to be an effective approach for localized PMME. Five-year survival rates have been achieved in 37% recently, while adjuvant therapy has not been proven to increase overall survival but plays a palliative role.
Subject(s)
Esophageal Neoplasms/pathology , Melanins/metabolism , Melanoma/pathology , Age of Onset , Diagnosis, Differential , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/therapy , Esophagectomy/methods , Female , Humans , Male , Melanoma/diagnosis , Melanoma/therapy , Middle Aged , Neoplasm Metastasis , Prognosis , Sex Factors , Survival RateABSTRACT
The authors report a rare case of intracranial yolk sac tumor in a 13-year-old boy with Down syndrome who presented with left hemiparesis. Admission MR imaging revealed a tumor in the right basal ganglia. Serum α-fetoprotein was markedly elevated. Yolk sac tumor was diagnosed radiologically and serologically. The standard therapy for intracranial yolk sac tumor is platinum-based chemotherapy with concomitant radiotherapy. However, the authors used reduced-dose chemotherapy and asynchronized radiotherapy because of the well-known low tolerance of patients with Down syndrome to chemotherapy. This treatment was successful with no complications. Blood cancers are frequently associated with Down syndrome, whereas solid tumors occur less frequently in these patients, and the risk of chemoradiotherapy is unclear. The results indicate that dose-reduction therapy can be effective for treatment of a brain tumor in a patient with Down syndrome.
Subject(s)
Antineoplastic Agents/administration & dosage , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Cisplatin/administration & dosage , Down Syndrome/complications , Endodermal Sinus Tumor/drug therapy , Endodermal Sinus Tumor/radiotherapy , Adolescent , Basal Ganglia/pathology , Biomarkers, Tumor/analysis , Brain Neoplasms/blood , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/etiology , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Endodermal Sinus Tumor/blood , Endodermal Sinus Tumor/diagnostic imaging , Endodermal Sinus Tumor/etiology , Humans , Magnetic Resonance Imaging , Male , Radiography , Radiotherapy, Adjuvant/methods , alpha-Fetoproteins/analysisABSTRACT
Although open-chest surgery is the mainstay treatment for esophageal cancer, the understanding of the context of the surgery differs in Japan and the rest of the world. Three-field lymph node dissection has been unique to Japan, although some reports on its benefits are emerging elsewhere. In addition to three-field lymph node dissection, various efforts are made during surgical procedures to reduce complications at high-volume Japanese healthcare institutions.
Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Lymph Node Excision/methods , HumansSubject(s)
Esophageal Neoplasms/surgery , Thoracotomy/methods , Humans , Lymph Node Excision/methodsABSTRACT
OBJECT: The Il13ra2 gene is often overexpressed in brain tumors, making Il13ra2 one of the vaccine targets for immunotherapy of glioma. In this study, using a mouse glioma model, the authors tested the hypothesis that vaccination using dendritic cells transfected with Il13ra2 mRNA induces strong immunological antitumor effects. METHODS: A plasmid was constructed for transduction of the mRNAs transcribed in vitro into dendritic cells. This was done to transport the intracellular protein efficiently into major histocompatibility complex class II compartments by adding a late endosomal/lysosomal sorting signal to the Il13ra2 gene. The dendritic cells transfected with this Il13ra2 mRNA were injected intraperitoneally into the mouse glioma model at 3 and 10 days after tumor cell implantation. The antitumor effects were estimated based on the survival rate, results of histological analysis, and immunohistochemical findings for immune cells. RESULTS: The group treated by vaccination therapy with dendritic cells transfected with Il13ra2 mRNA survived significantly longer than did the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing CD4+ and CD8+ T cells were found in the group vaccinated with dendritic cells transfected with Il13ra2 mRNA. CONCLUSIONS: These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with Il13ra2 mRNA for the treatment of malignant glioma.
Subject(s)
Brain Neoplasms/therapy , Cancer Vaccines/pharmacology , Dendritic Cells/transplantation , Genetic Therapy/methods , Glioma/therapy , Interleukin-13 Receptor alpha2 Subunit/genetics , Animals , Bone Marrow Cells/cytology , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cell Line, Tumor , Chloroquine/pharmacology , Dendritic Cells/immunology , Glioma/immunology , Glioma/pathology , Histocompatibility Antigens Class II/immunology , Immunophenotyping , Interleukin-13 Receptor alpha2 Subunit/immunology , Interleukin-13 Receptor alpha2 Subunit/metabolism , Male , Mice , Mice, Inbred C57BL , Neoplasm Invasiveness/pathology , Neoplasm Transplantation , Plasmids/pharmacology , RNA, Messenger/pharmacology , Signal Transduction/drug effects , Survival Rate , TransfectionABSTRACT
Squamous cell carcinoma of the esophagus (ESCC) has a poor prognosis among digestive tract cancers. Lymph node metastasis and distant metastasis are the major factors determining its prognosis. We used comparative genomic hybridization (CGH) to evaluate primary tumor lymph nodes and metastatic areas from ESCC patients in order to determine the relationship between abnormal chromosome regions and outcome. Tumor tissues and lymph nodes were collected from 51 patients with ESCC, and abnormal chromosome regions were detected by CGH. We searched for regions that were significantly more common in patients with lymph nodes metastases (n>/= 6) or distant metastases, and correlated those chromosomal changes with survival. Regions showing amplification in more than 65% of esophageal squamous cell cancers were as follows: 17q12 (90.2%), 17q21 (86.3%), 3q29 (82.4%), 3q28 (78.4%), 8q24.2 (76.5%), 22q12 (76.5%), 3q27 (74.5%), 8q24.3 (74.5%), 1q22 (70.6%), 5p15.3 (70.6%), 22q13 (70.6%), 3q26.3, 8q23, 8q24.1, 9q34, 11q13, 17p12, 17q25, 20q12, 20q13.1 (68.6%), 1q32, 1q42, and 20q13.2 (66.7%). Regions showing deletion in more than 50% of the tumors were as follows: Yp11.3 (62.7%), 3p26 (56.9%), Yq12 (54.9%), 13q21 (52.9%), 4q32 (51.0%), and 13q22 (51.0%). When Fisher's test was used to assess associations of these regions with metastases to lymph nodes, amplification at 2q12-14 (P= 0.012), 3q24-26 (P= 0.005), and 7q21-31 (P= 0.026) were significant. Survival was worse for patients with amplification at all 3 regions. In patients with distant organ metastases, amplification at 7p13-21 was significant (P= 0.008), and survival was worse. Chromosomal amplifications in ESCC at 2q12-14, 3q24-26, and 7q21-31 were associated with lymph node metastasis, while amplification at 7p13-21 was related to distant metastasis. Amplification at these regions correlated with worse survival. Genes involved in the phenotype of ESCC may exist in these regions. Identification of these genes is a theme for future investigation.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Chromosome Aberrations , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Gene Amplification/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/secondary , Comparative Genomic Hybridization , Female , Gene Deletion , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Metastasis , PrognosisABSTRACT
Squamous cell carcinoma (SCC) of the esophagus occasionally produces subepithelial extension (SEE) in the stroma below the non-cancerous epithelium. Little information on SEE has been obtained, therefore the purpose of the present study was to carry out a clinicopathological study using D2-40 immunostaining in 108 cases of superficial (mucosal and submucosal) SCC of the esophagus. SEE occurred in 24 cases (22.2%). The SEE was present in both mucosa and submucosa in 19 cases, but in five cases SEE was located in the mucosa. Lymphatic invasion of tumor cells was well determined on D2-40 immunostaining. In the SEE group lymphatic invasion was found in 15 cases, and in two cases there was lymphatic invasion in the lamina propria mucosa of the edge of SEE. In the SEE group 23 (95.8%) had infiltrative growth of tumor cells. Lymphatic invasion and growth pattern of tumor cells were statistically correlated with SEE. Lymph node metastases were found in 48 cases, but SEE was not correlated with nodal metastases statistically. In conclusion, esophageal SCC produces SEE from the early stage by infiltrative growth and lymphatic invasion of tumor cells. The detection of lymphatic invasion on D2-40 immunostaining in the mucosal edge of SEE is useful for evaluation of endoscopic mucosal resection tissue.
Subject(s)
Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Lymphatic Metastasis/pathology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal , Antibodies, Monoclonal, Murine-Derived , Carcinoma, Squamous Cell/metabolism , Endoscopy, Digestive System , Esophageal Neoplasms/metabolism , Female , Humans , Immunohistochemistry , Lymphatic Vessels/pathology , Male , Middle Aged , Mucous Membrane/metabolism , Mucous Membrane/pathologyABSTRACT
A 72-year-old female presented with a lump in the left superior-lateral eyelid. The magnetic resonance imaging showed a well-delineated mass in the left lacrimal gland. The tumor was isointense on both the T1 and T2 weighted images, and it was homogenously enhanced with Gd-DTPA. Surgery via the trans-cranial approach revealed a pinkish and elastic-hard tumor. Total resection was successfully performed. The hematoxilyn-eosin staining of the surgical specimen showed a dense infiltrate of lymphocytes, which were composed predominantly of small lymphocytes, centrocyte-like cells, monocytoid cells, and occasionally transformed lymphocytes. The immunohistochemical findings for CD20, CD3, UCHL-1, CD23, CD5, cyclinD1, and bcl-2 were compatible with Mucosa Associated Lymphoid Tissue (MALT)-type lymphoma. The patient received local radiation therapy (30 Gy/15 fractions). She remained in complete clinical remission of the disease about one and a half years after treatment.
Subject(s)
Eye Neoplasms/diagnosis , Lacrimal Apparatus , Lymphoma, B-Cell, Marginal Zone/diagnosis , Aged , Eye Neoplasms/radiotherapy , Female , Gadolinium DTPA , Humans , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Magnetic Resonance Imaging , Radiotherapy Dosage , Remission InductionABSTRACT
OBJECT: The receptor for hyaluronan-mediated motility (RHAMM) is frequently overexpressed in brain tumors and was recently identified as an immunogenic antigen by using serological screening of cDNA expression libraries. In this study, which was conducted using a mouse glioma model, the authors tested the hypothesis that vaccination with dendritic cells transfected with RHAMM mRNA induces strong immunological antitumor effects. METHODS: The authors constructed a plasmid for transduction of the mRNAs transcribed in vitro into dendritic cells, which were then used to transport the intracellular protein RHAMM efficiently into major histocompatibility complex class II compartments by adding a late endosomal-lysosomal sorting signal to the RHAMM gene. The dendritic cells transfected with this RHAMM mRNA were injected intraperitoneally into the mouse glioma model 3 and 10 days after tumor cell implantation. The antitumor effects of the vaccine were estimated by the survival rate, histological analysis, and immunohistochemical findings for immune cells. Mice in the group treated by vaccination therapy with dendritic cells transfected with RHAMM mRNA survived significantly longer than those in the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing T cells activated by CD4+, CD8+, and CD25+ were found in the group vaccinated with dendritic cells transfected with RHAMM mRNA. CONCLUSIONS: These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with RHAMM mRNA for the treatment of malignant glioma.