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Subcutaneous Tumors (subcutaneous + tumor)
Selected AbstractsCutaneous sclerosing perineurioma of the digitINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2006Toshitsugu Nakamura MD An 11-year-old Japanese girl noticed a small nodule, with mild tenderness, on the right index finger 5 years before visiting our outpatient clinic. She had no familial history of neurofibromatosis or past history of traumatic injury at the site of the tumor. Physical examination revealed a slightly elevated, subcutaneous, nodular tumor in the volar aspect between the proximal and distal interphalangeal joints of the digit (Fig. 1A). By magnetic resonance imaging examination, the tumor showed low density on both T1- and T2-weighted images, and was located just adjacent to the tendon with no invasive signs. The tumor was extirpated; at operation, it was well circumscribed and mobile without adhesion to adjacent tendon or nerve, and was easily removed. Figure 1. (a) Slightly elevated subcutaneous tumor (arrow) on the volar aspect of the right index finger. (b) gross appearance of the extirpated tumor, showing a well-circumscribed, whitish solid nodule Grossly, the tumor was a well-circumscribed, firm nodule (10 mm × 8 mm × 5 mm in size) (Fig. 1B). The cut surface was whitish, homogeneous, and solid without cystic lesions. Histologically, it was an unencapsulated, paucicellular dense, fibrous nodule with a concentric circular arrangement of collagen bundles (Fig. 2A). Amongst the fibrous bundles, a small number of ovoid/epithelioid or plump spindle cells were arranged in a corded, trabecular, or whorled (onion bulb-like) pattern (Fig. 2B); a storiform pattern was not noted. These cells were relatively uniform and had a somewhat elongated, slightly hyperchromatic nucleus with fine granular chromatin. Neither nuclear pleomorphism nor multinucleated cells were evident, and necrosis and mitotic figures were not observed. Periodic acid,Schiff (PAS) stain after diastase digestion highlighted the corded or whorled pattern of the tumor cells by encasing them. For immunohistochemical examination, formalin-fixed, paraffin-embedded serial tissue sections were stained by a labeled streptavidin,biotin method. The tumor cells were positive for vimentin and epithelial membrane antigen (EMA) (Fig. 3A), and negative for pan-cytokeratin, carcinoembryonic antigen (CEA), CD34, ,-smooth muscle actin, desmin, and CD68. Type IV collagen and laminin (Fig. 3B) were detected along the cords or whorls of the tumor cells, similar to the staining pattern of the diastase-PAS reaction. Schwann cells and axonal components, immunoreactive for S100 protein and neurofilament, respectively, were focally detected just adjacent to the cords or whorls, although the tumor cells per se did not express these proteins. Consequently, the tumor was found to be perineurial in origin and was diagnosed as cutaneous sclerosing perineurioma. Figure 2. (a) Low-power view of the tumor, showing an unencapsulated, paucicellular, dense, fibrous nodule with a concentric circular arrangement of collagen bundles (hematoxylin and eosin stain: original magnification, ×15). (b) Higher magnification of the tumor, showing ovoid or epithelioid cells arranged in cords or whorls in the abundant collagen bundles (hematoxylin and eosin stain: original magnification, ×150) Figure 3. Immunohistochemical profiles of the tumor. The tumor cells are positive for epithelial membrane antigen (a) and are surrounded by laminin (b) (original magnification, ×150) [source] Subcutaneous angioleiomyomas: Gray-scale and color Doppler sonographic appearancesJOURNAL OF CLINICAL ULTRASOUND, Issue 2 2006Vanesa Gomez-Dermit MD Abstract Purpose: To describe the gray-scale Doppler and sonographic features of a series of subcutaneous angioleiomyomas. Methods: The sonographic appearances of 10 pathologically proven angioleiomyomas were retrospectively reviewed; 4 in women and 6 in men, with an age range from 33 to 77 years. We evaluated size, shape, echo pattern, margins, location, relationships with adjacent structures, and vascularity. Examinations were performed using a multifrequency linear array transducer (9,11 MHz) connected to a Logiq 500 scanner (GE, Milwaukee, Wl). Results: All tumors were subcutaneous and located in the extremities (7 in the lower extremities, 3 in the upper extremities). The sizes ranged from 0.6 to 6.4 cm, with an average size of 2 cm. All of the lesions were hypoechoic with well-defined margins, and 9 were oval. Intratumoral calcifications were observed in two patients. Vascularity was easily detected in all of them, and 4 tumors had a clear vascular pedicle. The spectral Doppler analysis performed in 5 cases, revealing a low-resistance arterial waveform in 4 patients. Conclusions: Although angioleiomyomas are uncommon soft tissue tumors, the presence of a well-defined, hypoechoic, vascular subcutaneous tumor in the extremities should raise the possibility of such a diagnosis. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:50,54, 2006 [source] Antitumor effects of a recombinant fowlpox virus expressing Apoptin in vivo and in vitroINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Xiao Li Abstract Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. To explore the use of the Apoptin gene in cancer gene therapy, we constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV- Apoptin) and compared the tumor-killing activity of the recombinant virus with that of wild-type fowlpox virus in the human hepatoma cell line HepG2. We found that although cells were somewhat resistant to the basal cytotoxic effect of wild-type fowlpox virus, infection with vFV- Apoptin caused a pronounced, additional cytotoxic effect. Furthermore, cell death and disruption of tumor integrity were apparent in the vFV- Apoptin -infected cells. We also tested whether fowlpox virus-mediated expression of Apoptin in tumor cells could stimulate an antitumor effect by injecting aggressive subcutaneous tumors derived from H22 mouse hepatoma cells in C57BL/6 mice with vFV- Apoptin. We found that fowlpox virus-mediated intratumoral expression of the Apoptin gene can induce protective and therapeutic antitumor effects and significantly increase survival. Taken together, these data indicate that infection of tumors with fowlpox virus expressing Apoptin inhibits tumor growth, induces apoptosis and may be an effective cancer treatment. © 2006 Wiley-Liss, Inc. [source] Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugateINTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Monica Fabbrini Abstract The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e6, after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody-photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis-related pathologies. © 2005 Wiley-Liss, Inc. [source] Local regulation of human breast xenograft models,,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Jodie M. Fleming Breast cancer studies implant human cancer cells under the renal capsule, subcutaneously, or orthotopically and often use estrogen supplementation and immune suppressants (etoposide) in xenograft mouse models. However, cell behavior is significantly impacted by signals from the local microenvironment. Therefore, we investigated how the combinatorial effect of the location of injection and procedural differences affected xenograft characteristics. Patient-derived breast cancer cells were injected into mouse abdominal or thoracic mammary glands,±,estrogen and/or etoposide pretreatment. Abdominal xenografts had increased tumor incidence and volume, and decreased latency (P,<,0.001) compared to thoracic tumors. No statistically significant difference in tumor volume was found in abdominal xenografts treated,±,estrogen or etoposide; however, etoposide suppressed tumor volume in thoracic xenografts (P,<,0.02). The combination of estrogen and etoposide significantly decreased tumor incidence in both sites. In addition, mice treated,±,estradiol were injected orthotopically or subcutaneously with well-characterized breast cancer cell lines (MCF7, ZR75-1, MDA MB-231, or MCF10Ca1h). Orthotopic injection increased tumor volume; growth varied with estrogen supplementation. Location also altered methylation status of several breast cancer-related gene promoters. Lastly, vascularization of orthotopic tumors was significantly enhanced compared to subcutaneous tumors. These data suggest that optimal xenograft success occurs with orthotopic abdominal injections and illustrate molecular details of the compelling influence of the local microenvironment on in vivo models. J. Cell. Physiol. 224: 795,806, 2010. Published 2010 Wiley-Liss, Inc. [source] Metastasis-associated gene expression profile of liver and subcutaneous lesions derived from mouse pheochromocytoma cellsMOLECULAR CARCINOGENESIS, Issue 4 2008Shoichiro Ohta Abstract The development of metastatic cancer is associated with overexpression or downregulation of specific genes and cell regulatory pathways. Some of these genes and pathways may be involved in invasion and dissemination of tumor cells, while others may promote seeding, survival or growth of cells at specific distant sites. In this investigation, gene expression profiles of nonmetastasizing tumors generated by injecting mouse pheochromocytoma cells (MPCs) subcutaneously were compared to those of liver tumors generated by injecting the cells intravenously. Both were compared to the cultured parental cell line. Tumors in the liver have a route of spread, anatomical distribution, and growth environment similar to naturally metastasizing pheochromocytomas, while intravenous injection of cells bypasses the initial steps of metastasis occurring spontaneously from a primary tumor. Eight genes were upregulated in liver tumors, 15 in subcutaneous tumors and seven in both compared to the cultured cells. Using quantitative real-time PCR, expression of five genes (Metap2, Reck, S100a4, Timp2, and Timp3) was verified as significantly lower in liver tumors than in subcutaneous tumors. Downregulation of these genes has been previously been associated with malignancy of pheochromocytomas. These findings indicate that different microenvironments can differentially affect the expression of metastasis-related genes in pheochromocytomas, and that overexpression or underexpression of these genes need not be present when the tumor cells are initially disseminated. The hepatic localization of tumors formed by intravenously injected MPC cells and the tumors' gene expression profile resembling that of naturally occurring pheochromocytoma metastases support the use of this model to study pheochromocytoma metastasis. © 2007 Wiley-Liss, Inc. [source] Poor intercellular transport and absence of enhanced antiproliferative activity after non-viral gene transfer of VP22-P53 or P53-VP22 fusions into p53 null cell lines in vitro or in vivoTHE JOURNAL OF GENE MEDICINE, Issue 7 2005David Zavaglia Abstract Background The herpes simplex virus type 1 (HSV-1) VP22 protein has the property to mediate intercellular trafficking of heterologous proteins fused to its C- or N-terminus. We have previously shown improved delivery and enhanced therapeutic effect in vitro and in vivo with a P27-VP22 fusion protein. In this report, we were interested in studying the spread and biological activity of VP22 fused to the P53 tumor suppressor. Methods Expression of the VP22-P53 and P53-VP22 fusion proteins was shown by Western blot and intercellular spreading was monitored by immunofluorescence on transiently transfected cells. In vitro antiproliferative activity of wild-type (wt) P53 and P53-VP22 was assessed by proliferation assays and transactivating ability was studied by a reporter gene test and a gel-shift assay. Antitumor activity was also tested in vivo by intratumoral injections of naked DNA in a model of subcutaneous tumors implanted in nude mice. Results Our results show that the C-terminal fusion or the N-terminal P53-VP22 fusion proteins are not able to spread as efficiently as VP22. Moreover, we demonstrate that VP22-P53 does not possess any transactivating ability. P53-VP22 has an antiproliferative activity, but this activity is not superior to the one of P53 alone, in vitro or in vivo. Conclusions Our study indicates that a gene transfer strategy using VP22 cannot be considered as a universal system to improve the delivery of any protein. Copyright © 2005 John Wiley & Sons, Ltd. [source] Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesisCANCER, Issue 7 2008In-Kiu Kwon PhD Abstract BACKGROUND Type 1 cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) reportedly has exhibited antitumor properties, and its expression is down-regulated in many tumors. METHODS The authors recently demonstrated that PKG re-expression in metastatic colon carcinoma cells results in decreased tumorigenesis: In the current study, they addressed that mechanism. RESULTS Over-expression of PKG in SW620 cells produced smaller, more apoptotic subcutaneous tumors in athymic mice, but the observed effect of PKG expression on growth and apoptosis in vitro was minimal. Closer examination of the subcutaneous xenografts revealed highly vascular tumors produced by the parental SW620 cells, which contrasted greatly with the PKG-expressing tumors, in which cell growth was limited to "islands" surrounding CD31-positive cells. The idea that PKG expression was associated with reduced tumor angiogenesis was supported by decreased levels of vascular endothelial growth factor in these tumors compared with tumors that were derived from parental SW620 cells. Investigation of potential mechanisms revealed that PKG expression was associated with reduced levels of ,-catenin compared with parental cells. Moreover, this effect of exogenous PKG on ,-catenin expression in SW620 cells also occurred in vitro, where the decrease was associated with reduced T-cell factor-dependent transcription. CONCLUSIONS Together the findings indicated that PKG down-regulation in colon cancer cells is important for optimal tumor angiogenesis and that regulation of ,-catenin expression may be important to this process. Cancer 2008. © 2008 American Cancer Society. [source] Methionine-enkephalin secreted by human colorectal cancer cells suppresses T lymphocytesCANCER SCIENCE, Issue 3 2009Hitoshi Ohmori The role of methionine-enkephalin (MENK) as an immunomodulator in colorectal carcinomas (CRC) was examined. MENK was produced in CT26, IEC6A, Colo320, and HT29 CRC cell lines but not in IEC6 intestinal cells. MENK secretion was associated with tumorigenicity and metastasis of CRC cells in syngeneic rodent models. The MENK concentration in subcutaneous tumors of CT26 and IEC6A CRC cells exhibited an inverse correlation with the number of tumor-infiltrating T lymphocytes. MENK inhibited the growth of MOLT-4 T-lymphoblastic cells in a dose-dependent manner. Furthermore, it increased the phosphorylation level of c-Jun N-terminal kinase and induced apoptosis in MOLT-4 cells. MENK-induced apoptosis was abrogated by a c-Jun N-terminal kinase inhibitor. Immunohistochemical analysis revealed moderate to strong expression of MENK in 33 (54%) of 61 CRC. MENK expression was associated with Dukes' staging, nodal metastasis, and liver metastasis. The MENK concentration in tumor tissues was higher in Dukes' C cases than in Dukes' B cases. MENK expression was associated with tumor-infiltrating T lymphocytes, especially those belonging to the CD4+ subset. These findings suggest that MENK secreted by CRC cells caused escape of the host from the effects of immunity. (Cancer Sci 2009; 100: 497,502) [source] Local interferon-, gene therapy elicits systemic immunity in a syngeneic pancreatic cancer model in hamsterCANCER SCIENCE, Issue 3 2007Hidehiko Hara The interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis and immunomodulation. We previously examined the two antitumor mechanisms, taking advantage of the fact that IFN-, did not show cross-species activity in its in vivo effect. In a nude mouse subcutaneous xenograft model using human pancreatic cancer cells, the expression of human IFN-, effectively induced cell death of human pancreatic cancer cells, whereas mouse IFN-, augmented antitumor immunity by stimulation of natural killer cells. Here, we extended our investigation to a syngeneic pancreatic cancer model, so that the integrated antitumor activity of local IFN-, gene therapy, including the antiproliferative, proapoptotic, antiangiogeneic and immunomodulatory effects, can be evaluated rigorously. When a recombinant hamster IFN-, adenovirus was injected into syngeneic subcutaneous tumors of hamster pancreatic cancer (PGHAM-1) cells in Syrian hamster, tumor growth was significantly suppressed due to cell death and T cell- and natural killer cell-mediated antitumor immunity. Moreover, in this case, tumor regression was observed not only for the injected subcutaneous tumors but also for the untreated tumors both in the peritoneal cavity and at distant sites. No significant systemic toxicity was observed in the treated hamsters. Moreover, the subcutaneous rechallenge of PGHAM-1 cells was rejected in three of four cured hamsters from the initial tumor challenge. This study further demonstrated that local IFN-, gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its multiple mechanisms of antitumor activity and its lack of significant toxicity. (Cancer Sci 2007; 98: 455,463)) [source] | |||||||||||||