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Tumor Mass (tumor + mass)
Selected AbstractsEffect of ketoprofen in topical formulation on vascular endothelial growth factor expression and tumor growth in nude mice with osteosarcomaJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2004Kenshi Sakayama Abstract OST cells, a low metastatic cell line established from human osteosarcoma, were inoculated under the periosteum of the ossa cranii of nude mice. Four weeks later, tumors were percutaneously treated for an additional 4 weeks with a patch containing either placebo or ketoprofen (KP). In the placebo group, OST cells formed osteoid and invaded the cranial bone. Tumor mass weighed 3.54 g. Approximately 85% of cells within the tumor expressed proliferating cell nuclear antigen (PCNA), indicating that they were proliferating with a high mitotic activity. Many feeder vessels were located within the tumor. The majority of tumor cells expressed intensely vascular endothelial growth factor (VEGF). In the KP group, invasion of OST cells into the cranial bone was suppressed and the tumor mass was 47% of that of the placebo group. Approximately 65% of cells within the tumor were PCNA-negative, indicating that their growth was arrested. There were considerably fewer feeder vessels within the tumor in the KP group than in the placebo group. Only a small number of cells expressed VEGF. Based on these findings, we concluded that topical administration of KP to nude mice with osteosarcoma inhibited VEGF expression, reduced the development of feeder vessels for supply of nutrients and oxygen, and suppressed tumor growth. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Spontaneous apoptosis in chronic lymphocytic leukemia and its relationship to clinical and cell kinetic parametersCYTOMETRY, Issue 6 2001Gislaine B. Oliveira Abstract Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the suceptibility to apoptosis. Cytometry (Comm. Clin. Cytometry) 46:329,335, 2001. © 2001 Wiley-Liss, Inc. [source] Case of early ampullary cancer treated by endoscopic papillectomyDIGESTIVE ENDOSCOPY, Issue 2 2004Kei Ito We herein report a case of ampullary cancer in a 65-year-old man who underwent endoscopic papillectomy. Duodenoscopy revealed an exposed-type tumor mass at the ampulla of Vater. Histology of the biopsy specimen demonstrated well-differentiated adenocarcinoma. Endoscopic ultrasonography and intraductal ultrasonography showed a hypoechoic mass limited to the ampulla of Vater (clinical stage, T1). Endoscopic papillectomy was performed after informed consent was obtained. Histological examination of the resected specimen revealed adenocarcinoma limited to the ampulla of Vater (final stage, pT1). Both accurate preoperative T staging and proper histological evaluation of the resected specimen appear to justify endoscopic treatment of early ampullary cancer. [source] Isolation and characterization of epithelial progenitor cells from human fetal liverHEPATOLOGY RESEARCH, Issue 1 2008Yi-Nan Liu Aim:, Hepatic progenitor cells can serve as an alternative source of hepatocytes for the treatment of liver diseases. Methods:, We isolated and expanded the epithelial progenitor cells (EPC) from the human fetal liver and investigated the differentiation of EPC into hepatic cells by fluorescence-activated cell sorter (FACS), real-time polymerase chain reaction (PCR), immunofluorescence assay, western blotting, and periodic acid,Schiff staining. Results:, Isolated EPC possessed highly proliferative ability and subpassaged for more than 25 passages. Real-time PCR showed that EPC expressed liver epithelial markers (cytokeratin [CK]8 and CK18) and biliary-specific markers (CK7 and CK19). FACS analysis indicated that these cells were positive for CD117, CD147, CD90, CD44, human leucocyte antigen class I and CD71, but negative for CD34 and CD45. The EPCpossessed multipotential indicated by differentiating into osteoblasts and adipocytes; when subjected to the hepatic differentiation condition, EPC could be induced to hepatocyte-like cells, which expressed albumin, alpha-fetoprotein, and CK18 proteins. Two months after EPC transplantation, we observed that the grafted cells differentiated into hepatocyte-like cells and there was no observable tumor mass. Conclusion:, We have isolated and characterized the human fetal liver-derived EPC and these cells may serve as an ideal cell source for cell-replacement therapy of diseased livers. [source] Eleven-Year Experience in Diagnosis and Surgical Therapy of Right Atrial MassesJOURNAL OF CARDIAC SURGERY, Issue 1 2007Nezihi Kucukarslan M.D. A review of surgical experience with right atrial tumors in 11 patients from our institution has been presented in this article. Methods: Eleven cases, operated for a tumor mass in the right atrium in our institution between January 1993 and December 2004, were retrospectively reviewed for their clinical presentation, diagnostic workup, method of surgical procedure, and histopathologic findings. Electrocardiogram, transthoracic, and transesophageal echocardiography, computerized tomography, and nuclear magnetic resonance imaging were available for all patients during the diagnostic evaluation. Surgical procedure notes, photos, and file recordings were reviewed when available. The surgeons were also interviewed when necessary. Results: Right atrial tumors were diagnosed in 11 patients (6 males and 5 females). The average age of the patients was 34 ± 11 years (ranging between 21 and 65 years). The histopathological examination of the surgically removed specimen revealed a benign tumor in eight patients (73%), and a malignant process in three (23%). In eight patients with a benign tumor, atrial myxoma was the leading cause in half of the cases. Hydatid cyst (n = 2), lipoma (n = 1), and right atrial thrombus (n = 1) were detected in the remaining four patients. One patient died of heart failure after surgery. The diameters of the excised masses were 2 ± 0.5 cm versus 7 ± 1 cm. Conclusions: Tumors of the right atrium are rarely seen, and necessitate a unique attention during the process of diagnosis and surgical treatment. We present our surgical experience of 11 patients with right atrial mass. The differentiation of the right atrial tumors with the diagnostic tools before surgery, the determination of the spreading, and the structural properties of the mass may designate surgical approach and prognosis. [source] Elevated serum level and gene polymorphisms of TGF-,1 in gastric cancerJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2008Xue Li Abstract Transforming growth factor (TGF)-,1, as a candidate tumor marker, is currently of interest. In this study, serum TGF-,1 levels in gastric cancer (GC) patients and healthy volunteers were measured using enzyme-linked immunosorbent assay (ELISA). In addition, single nucleotide polymorphisms (SNPs) of the TGF-,1 gene at codon 10 and codon 25 were identified by means of amplification refractory mutation system,polymerase chain reaction (ARMS-PCR) and sequence analysis. Our results indicated that serum concentrations of TGF-,1 in GC patients were significantly higher than those in the control, and positively correlated with tumor mass, invasion, metastasis, and clinical stage. The serum TGF-,1 levels of patients recovering from radical resection were markedly lower than those before surgery. Meanwhile, no deoxyribonucleic acid (DNA) sequence variation at codon 25 of the TGF-,1 gene was found and a TGF-,1 gene polymorphism at codon 10 did not show obvious correlations with either TGF-,1 expression or clinicopathological parameters of GC. Our evidence suggested that serum concentration of TGF-,1 might be a novel tumor marker for GC and the polymorphisms of TGF-,1 gene did not play a role as a determinant of serum TGF-,1 concentration or as a genetic risk factor in the gastric carcinogenesis and progression. J. Clin. Lab. Anal. 22:164,171, 2008. © 2008 Wiley-Liss, Inc. [source] Peripheral ameloblastoma of the gingiva: the importance of diagnosisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2005Pía López-Jornet Abstract Background: Peripheral ameloblastoma is an extremely rare epithelial odontogenic tumor, limited to the soft tissues of the gums or oral mucosa. Although the lesion is benign, it may be locally aggressive. Methods: The present study describes the case of a 31-year-old male presenting a firm, symptomless tumor mass of irregular appearance and measuring approximately 12 mm in diameter, located in the distal zone of 4.7. Results: An excision biopsy was performed. The lesion was covered with hyperplastic squamous epithelium, with islets of epithelial cells located at subepithelial level. The cells in the peripheral zone adopted a palisade distribution, and presented the appearance of a lax reticulum at central level. A fibroblastic stroma was observed between the islets. The diagnosis was peripheral ameloblastoma. Conclusions: Although the origin of the lesion remains unclear, it is able to recur and undergo malignant transformation. Consequently, peripheral ameloblastoma should not be viewed as a harmless mass. [source] Effect of ketoprofen in topical formulation on vascular endothelial growth factor expression and tumor growth in nude mice with osteosarcomaJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2004Kenshi Sakayama Abstract OST cells, a low metastatic cell line established from human osteosarcoma, were inoculated under the periosteum of the ossa cranii of nude mice. Four weeks later, tumors were percutaneously treated for an additional 4 weeks with a patch containing either placebo or ketoprofen (KP). In the placebo group, OST cells formed osteoid and invaded the cranial bone. Tumor mass weighed 3.54 g. Approximately 85% of cells within the tumor expressed proliferating cell nuclear antigen (PCNA), indicating that they were proliferating with a high mitotic activity. Many feeder vessels were located within the tumor. The majority of tumor cells expressed intensely vascular endothelial growth factor (VEGF). In the KP group, invasion of OST cells into the cranial bone was suppressed and the tumor mass was 47% of that of the placebo group. Approximately 65% of cells within the tumor were PCNA-negative, indicating that their growth was arrested. There were considerably fewer feeder vessels within the tumor in the KP group than in the placebo group. Only a small number of cells expressed VEGF. Based on these findings, we concluded that topical administration of KP to nude mice with osteosarcoma inhibited VEGF expression, reduced the development of feeder vessels for supply of nutrients and oxygen, and suppressed tumor growth. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Melatonin suppresses tumor angiogenesis by inhibiting HIF-1, stabilization under hypoxiaJOURNAL OF PINEAL RESEARCH, Issue 2 2010Shi-Young Park Abstract:, Angiogenesis is an important mediator of tumor progression. As tumors expand, diffusion distances from the existing vascular supply increases, resulting in hypoxia in the cancer cells. Sustained expansion of a tumor mass requires new blood vessel formation to provide rapidly proliferating tumor cells with an adequate supply of oxygen and nutrients. The key regulator of hypoxia-induced angiogenesis is the transcription factor known as hypoxia-inducible factor (HIF)-1. HIF-1, is stabilized by hypoxia-induced reactive oxygen species (ROS) and enhances the expression of several types of hypoxic genes, including that of the angiogenic activator known as vascular endothelial cell growth factor (VEGF). In this study, we found that melatonin, a small lipophilic molecule secreted primarily by the pineal gland, destabilizes hypoxia-induced HIF-1, protein levels in the HCT116 human colon cancer cell line. This destabilization of HIF-1, resulted from the antioxidant activity of melatonin against ROS induced by hypoxia. Moreover, under hypoxia, melatonin suppressed HIF-1 transcriptional activity, leading to a decrease in VEGF expression. Melatonin also blocked in vitro tube formation and invasion and migration of human umbilical vein endothelial cells induced by hypoxia-stimulated conditioned media of HCT116 cells. These findings suggest that melatonin could play a pivotal role in tumor suppression via inhibition of HIF-1-mediated angiogenesis. [source] The role of thrombin in gliomasJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2005Y. HUA Summary.,Background:,In a previous study we found that intracerebral infusion of argatroban, a specific thrombin inhibitor, reduces brain edema and neurologic deficits in a C6 glioma model. Objectives:,To examine the role of thrombin in gliomas and whether systemic argatroban administration can reduce glioma mass and neurologic deficits and extend survival time in C6 and F98 gliomas. Methods:,The presence of thrombin in human glioblastoma samples and rat C6 glioma cells (in vitro and in vivo) was assessed using immunohistochemistry. The effect of thrombin on C6 cell proliferation in vitro was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The role of thrombin in vivo was assessed in rat C6 and F98 glioma cell models using argatroban, a thrombin inhibitor. The effects of argatroban on tumor mass, neurologic deficits and survival time were investigated. Results:,Thrombin immunoreactivity was found in cultured rat C6 glioma cells and human glioblastomas. Thrombin induced C6 cell proliferation in vitro. In C6 glioma, argatroban reduced glioma mass (P < 0.05) and neurologic deficits (P < 0.05) at day 9. In F98 glioma, argatroban prolonged survival time (P < 0.05). Conclusion:,These results suggest that thrombin plays an important role in glioma growth. Thrombin may be a new therapeutic target for gliomas. [source] Combination of Er:YAG laser and photodynamic therapy in the treatment of nodular basal cell carcinomaLASERS IN SURGERY AND MEDICINE, Issue 2 2008Roman, mucler PhD Abstract Backgrounds and Objectives Photodynamic therapy (PDT), via topical aminolevulinic acid (ALA) is an effective treatment for basal cell carcinomas not exceeding a depth of 2 mm. This limits the treatment of basal cell carcinoma (non-melanoma skin cancer) to superficial forms and nodular therapy (only in aesthetically desired locations). This paper addresses the effectiveness of reducing tumor mass via initial Er:YAG laser ablation to depths that are therapeutically responsive to PDT with ALA. Study Design/Materials and Methods This study compared three methods for the treatment of recurring nodular basal cell carcinomas (r nBCC). Method A utilized PDT with topical application of ALA methyl ester, method B with solitary Er:YAG laser ablation, and method C combined Er:YAG laser ablation reducing tumor size below 2 mm (method B) with subsequent ALA methyl ester PDT (method A). All three methods were used to treat to each patient, all subjects presenting with three or more basal cell carcinomas in order to eliminate differences in patient responsiveness to treatment. Patients were monitored and interviewed at 3, 6, and 12 month intervals to examine the progress of tumor elimination, aesthetic results as well as the patient's preference of treatment method. In all, 286 patients were treated, of whom 194 were checked at the prescribed intervals and then evaluated. Results Statistically, the combination therapy demonstrated the most effective treatment at all time intervals, with a final efficacy of 98.97% versus 94.85% (PDT only) and 91.75% (Er:YAG laser only). The combined method also provided the best aesthetic results (scale: 1,best; 4,worst) of 1.23±1.23, compared to 1.67±0.76 (PDT only) and 1.83±0.95 (Er:YAG laser only). Conclusions Although 67% patients preferred solitary Er:YAG laser treatment over the PDT method (20%) and the combined treatment (13%), because of the simplicity of the treatment, the combination therapy has proven to be both clinically and aesthetically superior. Solitary Er:YAG laser ablation will remain however a fast, effective, and economical treatment alternative for simple manifestations of superficial basal cell carcinoma and has replaced PDT for uncomplicated cases at our facility. The combination of Er:YAG laser ablation and ALA,PDT aspires to be therapy of choice for BCC. Lesers Surg. Med. 40:153,158, 2008. © 2008 Wiley-Liss, Inc. [source] Human rectal adenocarcinoma: Demonstration of 1H-MR spectra in vivo at 1.5 TMAGNETIC RESONANCE IN MEDICINE, Issue 4 2002A.S.K. Dzik-Jurasz This study was designed to determine whether 1H-MR spectra of locally advanced human rectal adenocarcinoma could be acquired in vivo at 1.5 T. Despite the relatively large size of these neoplasms, only six out of 21 tumors accommodated a voxel size of 8 cm3. This was due to air pockets within the tumor mass, which limited voxel positioning. Localized proton spectra were acquired at short (20 ms) and long (135 ms) echo times (TEs) using a single-voxel technique. The most commonly detected metabolites were choline and lipid. Magn Reson Med 47:809,811, 2002. © 2002 Wiley-Liss, Inc. [source] Pleomorphic adenoma with extensive necrosis: report of two casesORAL DISEASES, Issue 1 2004YK Chen Pleomorphic adenoma (PA) is the most common neoplasm for both the major and minor salivary glands. While PA is occasionally associated with cystic change or hemorrhage necrosis, spontaneous infarction appears to be very uncommon. We report two unusual cases of extensive necrosis of PA; one occurred in the palate with the necrotic tumor mass slipping into the oral cavity. This phenomenon, possibly associated with incision biopsy, has never been described previously. A second case, arising in the parotid with spontaneous tumor necrosis, poses some dilemma in differential diagnosis. [source] Metaplastic breast carcinoma with melanocytic differentiationPATHOLOGY INTERNATIONAL, Issue 9 2009Antonia Bendic Metaplastic carcinoma of the breast is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Metaplastic breast carcinoma composed of both epithelial and melanocytic elements is rare, and only seven cases have been reported so far. Reported herein is the case of a 38-year-old woman with a nodular mass in her left breast suspicious of malignancy, discovered during routine ultrasound examination. After histological and immunohistochemical examination of the resected tumor mass, initial diagnosis was collision tumor: ductal invasive carcinoma and metastatic melanoma. The patient underwent quadrantectomy, chemotherapy and radiotherapy. At 6 years follow up the patient was alive and healthy, without local recurrence or metastases. After revising slides and the literature, in addition to patient follow up, it was concluded that this case represents metaplastic carcinoma with melanocytic differentiation. [source] Pulmonary tumor thrombotic microangiopathy resulting from metastatic signet ring cell carcinoma of the stomachPATHOLOGY INTERNATIONAL, Issue 6 2007Naomi Sakashita Pulmonary tumor thrombotic microangiopathy is an unusual malignancy-related respiratory complication characterized by multiple microthrombi and intimal myofibroblast proliferation. Its clinical manifestation is subacute respiratory failure with pulmonary hypertension. Herein is reported a case of pulmonary tumor thrombotic microangiopathy associated with gastric signet ring cell carcinoma. A 51-year-old woman with gastric cancer died of subacute respiratory failure. Autopsy showed gastric signet ring cell carcinoma with diffuse metastasis of pulmonary lymphatics and pleurae; every organ examined lacked a space-occupying tumor mass. Histologically, proliferated intimal myofibroblasts obliterated most of the pulmonary vascular lumen, and a few stenosed vascular lumina contained cancer cells. In addition, pulmonary vasculature associated with intimal proliferation contained microthrombi. Most cancer cells in the stomach and pulmonary lymphatics were typical signet ring cells, whereas those in vascular lesions were cells of poorly differentiated adenocarcinoma without mucous production. Consistent with a previous report, the latter expressed vascular endothelial growth factor (VEGF) and tissue factor (TF). The proliferated intimal myofibroblasts also expressed type 2A serotonin receptor (5-HT2A). These findings suggest that local expression of VEGF, TF, and 5-HT2A may be linked to the pathogenesis of this unusual pulmonary complication. [source] Neurofibromatosis type 1-associated unusual pleomorphic astrocytoma displaying continual malignant progressionPATHOLOGY INTERNATIONAL, Issue 7 2001Hideaki Yokoo Patients with neurofibromatosis type 1 (NF1) often have gliomas as a complication, most of which are benign pilocytic astrocytomas which have arisen in optic pathways. In the present case, a 17-year-old girl (at death) with stigmata of NF1, initially had a bulky tumor mass in the left thalamus, developing into the lateral ventricle, at 13 years of age. Partially resected tissue samples showed pleomorphic astrocytoma with abundant xanthoma cells and degenerative structures such as Rosenthal fibers (RF) and eosinophilic granular bodies. Fine eosinophilic granules identical to RF, both immunophenotypically and ultrastructurally, were also seen. The residual tumor was subtotally resected 6 months later, and the tumor histology was essentially similar as before, accompanying the regenerative structures; this was believed to be a good prognostic indicator. However, several anaplastic features such as mitosis, necrosis and vascular proliferation appeared even in areas rich in the regenerative structures. After a 2-year, disease-free interval, multiple tumor relapse occurred in June 1997. Partially resected tumor tissues were composed of monotonous small anaplastic cells with prominent proliferative activity. Surprisingly, the tumor cells had retained eosinophilic granules within the cell bodies. Postoperative chemotherapy with procarbazine, MCNU and vincristine (PCV) suppressed the residual tumor dramatically, but the regrowing tumor finally became uncontrollable, leading to the patient's death. TP53 mutation was not detected, while p27 immunopositivity was constantly high during malignant progression, suggesting acquisition of proliferative activity to overcome p53 and p27 inhibitory functions. A review of previously published reports failed to reveal any cases of this type. [source] A differential proteome in tumors suppressed by an adenovirus-based skin patch vaccine encoding human carcinoembryonic antigenPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2005Chun-Ming Huang Abstract We created an anti-tumor vaccine by using adenovirus as a vector which contains a cytomegalovirus early promoter-directed human carcinoembryonic antigen gene (AdCMV-hCEA). In an attempt to develop the skin patch vaccine, we epicutaneously vaccinated Balb/c mice with AdCMV-hCEA. After nine weeks post-immunization, vaccinated mice evoked a robust antibody titer to CEA and demonstrated the capability of suppressing in vivo growth of implanted murine mammay adenocarioma cell line (JC-hCEA) tumor cells derived from a female Balb/c mouse. Proteomic analysis of the tumor masses in the non-vaccinated naïve and vaccinated mice reveal that six proteins change their abundance in the tumor mass. The levels of adenylate kinase 1, ,-enolase, creatine kinase M chain, hemoglobin beta chain and prohibitin were statistically increased whereas the level of a creatine kinase fragment, which is undocumented, was decreased in the tumor of vaccinated mice. These proteins may provide a vital link between early-stage tumor suppression and immune response of skin patch vaccination. [source] Juvenile Nasopharyngeal Angiofibroma: Management and TherapyTHE LARYNGOSCOPE, Issue 4 2001Arne W. Scholtz MD Abstract Objective To conduct a review of contemporary approaches on the diagnostic-preoperative, operative, and postoperative methods in the management of juvenile nasopharyngeal angiofibroma (JNA). Study Design Retrospective study of 14 cases of JNA resection at the Department of Otorhinolaryngology, University of Innsbruck (Innsbruck, Austria) between 1987 and 1998. Methods Data was obtained for each patient regarding age, presenting symptoms, duration of symptoms, biopsy findings, tumor location, administration of preoperative angiography and embolization, and surgical approach. The follow-up period ranged from 1 to 13 years. Results Based on the histological evaluation by the preoperative biopsy and the tumor location, several surgical approaches were applied. A transnasal endoscopic procedure was employed in seven cases. The preoperative embolization and the intranasal approach with the potassium titanyl phosphate laser minimized blood loss. The recurrence rate was at a low of 15%. Conclusion The surgical approach should be determined by tumor location, tumor size, and effectiveness of tumor embolization. For patients with JNA with tumor extension involving the nasopharynx, the nasal cavity, the paranasal sinuses, and the pterygopalatine fossa, the transnasal endoscopic technique offers a minimally invasive resection of the entire tumor mass with minimal morphological disturbance. [source] Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: report of a rare case and review of the literatureAPMIS, Issue 3 2009CAFER ADIGUZEL Primary effusion lymphoma (PEL) is a very rare type of lymphoma usually confined to the body cavities predominantly in immunosupressed patients infected with human herpes virus 8 (HHV-8). The new term for HHV-8 independent PEL is HHV8-unrelated PEL-like lymphoma. We describe an 89-year-old human immunodeficiency virus (HIV)-negative male patient with HHV8-unrelated PEL-like lymphoma in the pleura. No hepatosplenomegaly or lymphadenopathy was detected. Chest radiography and computed tomography revealed right pleural effusion, but no evidence of tumor mass or lymph node enlargement. Cytological analysis of the pleural effusion revealed a high-grade lymphoma with round nuclei, prominent nucleoli and abundant cytoplasm with immunophenotypes positive for CD45, CD30, CD38, CD7 and CD71. Because of the advanced age, no chemotherapy was given. Effusion resolved spontaneously. One year after the diagnosis, a new pleural effusion developed at the left side. Following thoracentesis and pleurodesis, the patient remained in complete remission for 40 months. To date, 30 cases of HHV8-unrelated PEL-like lymphoma/HIV negative have been reported in the literature. The outcome of the HHV8-unrelated PEL-like lymphoma patients who were HIV negative seems to be better than HIV- and HHV-8-positive PEL. [source] Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in miceCANCER SCIENCE, Issue 8 2009Yuusuke Akao Oral administration of hot-water extract of Spirulina, cyanobacterium Spirulina platensis, leads to augmentation of NK cytotoxicity in humans. Here, we applied to syngeneic tumor-implant mice (C57BL/6 versus B16 melanoma) Spirulina to elucidate the mechanism of raising antitumor NK activation. A B16D8 subcell line barely expressed MHC class I but about 50% expressed Rae-1, a ligand for NK activation receptor NKG2D. The Rae-1-positive population of implant B16 melanoma was effectively eliminated in the tumor mass progressed in mice. This antitumor activity was induced in parallel with IFN-, and abolished in mice by treatment with asialoGM-1 but not CD8, Ab, suggesting the effector is NK cell. NK cell activation occurred in the spleen of wild-type mice medicated with Spirulina. This Spirulina-mediated enhanced NK activation was abrogated in MyD88 ,/, mice but not in TICAM-1 ,/, mice. The NK activating properties of Spirulina depending on MyD88 were confirmed with in vitro bone marrow-derived dendritic cells expressing TLR2/4. In D16D8 tumor challenge studies, the antitumor effect of Spirulina was abolished in MyD88 ,/, mice. Hence, orally administered Spirulina enhances tumoricidal NK activation through the MyD88 pathway. Spirulina exerted a synergistic antitumor activity with BCG,cell wall skeleton, which is known to activate the MyD88 pathway via TLR2/4 with no NK enhancing activity. Spirulina and BCG,cell wall skeleton synergistically augmented IFN-, production and antitumor potential in the B16D8 versus C57BL/6 system. We infer from these results that NK activation by Spirulina has some advantage in combinational use with BCG,cell wall skeleton for developing adjuvant-based antitumor immunotherapy. (Cancer Sci 2009) [source] Mechanism and biological significance of CD44 cleavageCANCER SCIENCE, Issue 12 2004Osamu Nagano There are multiple steps in the metastasis of cancer cells. Tumor cells must first detach from the tumor mass and invade the surrounding extracellular matrix (ECM). In this step, cell surface adhesion molecules play an important role in the interaction between the cells and their microenvironments. CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and is implicated in a wide variety of physiological and pathological processes. Recently, proteolytic cleavages of CD44 have been emerging as key regulatory events for the CD44 dependent cell-matrix interaction and signaling pathway. CD44 undergoes sequential proteolytic cleavages in the ectodomain and intramem-branous domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. The ectodomain cleavage of CD44 is triggered by multiple stimulations and contributes to the regulation of cell attachment to and migration on HA matrix. The ectodomain cleavage subsequently induces the intramembranous cleavage, which is mediated by presenilin (PS)-dependent y-secre-tase. The intramembranous cleavage generates CD44ICD, which acts as a signal transduction molecule; it is translocated to the nucleus and activates transcription. An understanding of the underlying mechanism of these cleavages of CD44 could provide novel therapeutic targets for cancer cell invasion and metastasis. [source] In vivo and in vitro Interactions between Human Colon Carcinoma Cells and Hepatic Stellate CellsCANCER SCIENCE, Issue 12 2000Sadatoshi Shimizu Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed ,-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF),, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-, had no effect. LM-H3 cells expressed PDGF receptors-, and -, and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis. [source] Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human ,-Fetoprotein GeneCANCER SCIENCE, Issue 3 2000Michito Kunitomi We constructed a plasmid containing human ,-fetoprotein (AFP) promoter/enhancer to direct the cell type-specific expression of diphtheria toxin fragment A (DTA), designated as pAF-DTA, to AFP-producing hepatocellular carcinoma cells. The transfection was carried out with cationic liposomes (DMRIE-C) and the expression of the DTA gene was confirmed by a northern blot analysis. When pAF-DTA was transfected, the growth of AFP-positive HuH-7 cells was inhibited, whereas growth inhibition was not observed in AFP-negative MKN45 cells. In this experiment, the secretion of AFP was similarly suppressed, but the secretion of carcinoembryonic antigen from MKN45 was not altered. pAF-DTA could also exert its growth inhibitory effect on PLC, a cell line with a low level of AFP. However, no inhibitory effect of pAF-DTA was observed on the proliferation of primary hepatocyte cells. Furthermore, transfection experiments in which HuH-7 and splenic stromal cells were co-cultured revealed the growth inhibition by pAF-DTA to be selective in HuH-7 cells. Finally, the growth of HuH-7 transplanted on BALB/c nu/nu mice was inhibited by the direct injection of pAF-DTA/liposome complex into a tumor mass. These results suggest that use of pAF-DTA may be potentially useful as a novel approach for the selective treatment of tumor cells producing AFP even at low levels, without affecting other types of cells. [source] Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal diseaseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Francesca Avogadri Abstract Salmonella typhimurium is a facultative anaerobic bacterium able to multiply preferentially in tumors and inhibit their growth. The mechanisms through which Salmonella exerts its anti-cancer properties are not fully understood. We recently showed that intra-tumoral Salmonella injection results not only in the regression of even bulky tumor masses, but also impacts on the growth of distant untreated lesions. Here we describe how Salmonella exerts its systemic anti-cancer effects and means to potentiate them. The outburst of an early inflammatory reaction in the treated tumor promotes the development of an immunostimulatory cytokine environment both locally and in the draining lymph node. Within the next 10,days, an efficient cross-presentation of endogenous tumor antigens by dendritic cells at the tumor-draining lymph node leads to the priming of effective anti-tumor CD8+ T cell responses. This potentially broadly reactive T cell repertoire can be directed to other pre-established melanomas by low-dose radiotherapy enhancing the Salmonella anti-cancer effect. We demonstrate that Salmonella -based therapy coupled to low-dose radiotherapy dampens tumor immune escape mechanisms at different levels and allows controlling systemic disease in a CD8+ T cell-dependent manner. [source] Natural history and long-term outcome of cardiac rhabdomyomas detected prenatallyPRENATAL DIAGNOSIS, Issue 4 2004Vlasta Fesslova Abstract Objectives To analyse the data of fetal cases with rhabdomyomatosis, the growth of masses in utero, and the relative outcome. Material and Methods Thirteen cases of cardiac/pericardial tumours with characteristics suggesting rhabdomyomatosis were found in our centre on fetal echocardiography, five before 24 wg (group A) and eight (group B) at 25 to 36 wg. Four patients terminated the pregnancy, nine continued the pregnancy and were followed-up until delivery and after birth (median postnatal follow-up of 4.2 years, range 18 months,16 years). Results In six/nine cases that continued the pregnancy (66.7%), the growth of smaller tumor masses was proportional with gestational age until 30 to 32 wg and was stable after that. In three cases, larger masses grew disproportionally and other small masses were revealed, causing a partial obstruction of outflow tracts. After birth, no case required surgery and no serious rhythm problems occurred. Cardiac masses regressed at least partially in all cases. Tuberous sclerosis was diagnosed in 9/11 cases (81.1%) investigated by magnetic resonance imaging in utero or postnatally. One case also had bilateral polycystic kidneys. Conclusions Multiple and larger noduli progressed disproportionally in utero, until 30 to 36 wg. No relevant cardiac problems occurred after birth and the masses regressed in all cases. The high frequency of association with tuberous sclerosis is confirmed in our series. Copyright © 2004 John Wiley & Sons, Ltd. [source] A differential proteome in tumors suppressed by an adenovirus-based skin patch vaccine encoding human carcinoembryonic antigenPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2005Chun-Ming Huang Abstract We created an anti-tumor vaccine by using adenovirus as a vector which contains a cytomegalovirus early promoter-directed human carcinoembryonic antigen gene (AdCMV-hCEA). In an attempt to develop the skin patch vaccine, we epicutaneously vaccinated Balb/c mice with AdCMV-hCEA. After nine weeks post-immunization, vaccinated mice evoked a robust antibody titer to CEA and demonstrated the capability of suppressing in vivo growth of implanted murine mammay adenocarioma cell line (JC-hCEA) tumor cells derived from a female Balb/c mouse. Proteomic analysis of the tumor masses in the non-vaccinated naïve and vaccinated mice reveal that six proteins change their abundance in the tumor mass. The levels of adenylate kinase 1, ,-enolase, creatine kinase M chain, hemoglobin beta chain and prohibitin were statistically increased whereas the level of a creatine kinase fragment, which is undocumented, was decreased in the tumor of vaccinated mice. These proteins may provide a vital link between early-stage tumor suppression and immune response of skin patch vaccination. [source] Manipulative therapy of secondary lymphedema in the presence of locoregional tumorsCANCER, Issue 4 2008Ximena A. Pinell BA Abstract BACKGROUND. Complete decongestive therapy (CDT), including manual lymphatic drainage (MLD) is a manipulative intervention of documented benefit to patients with lymphedema (LE). Although the role of CDT for LE is well described, to the authors' knowledge there are no data regarding its efficacy for patients with LE due to tumor masses in the draining anatomic bed. Traditionally, LE therapists are wary of providing therapy to such patients with ,malignant' LE for fear of exacerbating the underlying cancer, and that the obstruction will render therapy less effective. In the current study, the authors' experience providing CDT for such patients is discussed. METHODS. Cancer survivors with LE were referred to therapists at 2 Atlanta-area clinics. CDT consists of treatment (Phase 1) and maintenance phases (Phase 2). During Phase 1, the patient undergoes manipulative therapy and bandaging daily until the LE reduction plateaus; at that point, Phase 2 (self-care) begins. At the beginning and end of Phase 1, LE is quantified and differences in girth volume calculated. The results for patients completing Phase 1 therapy for LE in the presence of locoregional masses were compared with results for patients with LE in the absence of such disease. Both volume reduction of the affected limb and number of treatments to plateau were analyzed. RESULTS. Between January 2004, and March 2007, LE of 82 limbs in 72 patients was treated with CDT and Phase 1 was completed. The median number of treatments to plateau was 12 (range, 4,23 treatments); the median limb volume reduction was 22% (range, ,23 to 164%). Nineteen limbs (16 patients) with associated chest wall/axillary or pelvic/inguinal tumors had nonsignificant difference in LE reduction (P = .75) in the presence of significantly more sessions to attain plateau (P = .0016) compared with 63 limbs in 56 patients without such masses. CONCLUSIONS. Patients with LE may obtain relief with CDT regardless of whether they have locoregional disease contributing to their symptoms. However, it will likely take longer to achieve that effect. Manipulative therapy of LE should not be withheld because of persistent or recurrent disease in the draining anatomic bed. Cancer 2008. © 2007 American Cancer Society. [source] Enhanced Growth Inhibition of Hepatic Multicellular Tumor Spheroids by Lactosylated Poly(ethylene glycol)-siRNA Conjugate Formulated in PEGylated PolyplexesCHEMMEDCHEM, Issue 9 2007Motoi Oishi Prof. Abstract PEGylated polyplexes (lac-PEGylated polyplexes) composed of poly(L -lysine) and lactosylated poly(ethylene glycol)-small interfering RNA conjugate, which inhibits the RecQL1 gene product, were revealed to show an appreciable growth inhibition of multicellular HuH-7 spheroids (human hepatocarcinoma cell lines) for up to 21 days (IC50=6,nM); this system used as an in,vitro three-dimensional (3D) model mimicking the in,vivo biology of tumors. The PEGylated polyplexes thus prepared had a size of approximately 110,nm with clustered lactose moieties on their periphery as targeting ligands for the asialoglycoprotein-receptor-expressing HuH-7 cells. In contrast, OligofectAMINE/siRNA (cationic lipoplex) was observed to have almost no growth-inhibitory effect against HuH-7 spheroids, even though the lipoplex showed a stronger growth-inhibitory effect than the lac-PEGylated polyplexes on conventional monolayer-cultured HuH-7 cells. The FITC-tagged conjugate in the lac-PEGylated polyplexes showed smooth penetration into the HuH-7 spheroids compared with that in the lipoplexes, as observed by confocal fluorescence-scanning microscopy. This indicates that the small size of approximately 100,nm and the reduced nonspecific interaction due to the nonionic and hydrophilic lactosylated PEG layer contributes to the smooth penetration of the PEGylated polyplexes into the spheroid interior, eventually facilitating their uptake into the cells composing the spheroids. Cellular apoptosis indicating programmed cell death was also observed in the HuH-7 spheroids treated with the PEGylated polyplexes, revealing that the observed growth inhibition was indeed induced by the RNAi of the RecQL1 siRNA. These data suggest that the smart PEGylated polyplexes can indeed penetrate into the multiple cell layers of 3D tumor masses in,vivo, exerting therapeutic effects through the RNAi. [source] | ||||||||||||||||||||||||||||