National Cancer Institute®
Last Modified: July 1, 2002
UI - 12021352
AU - Zhou FC; Zhang YJ; Deng JH; Wang XP; Pan HY; Hettler E; Gao SJ
TI - Efficient infection by a recombinant Kaposi's sarcoma-associated herpesvirus cloned in a bacterial artificial chromosome: application for genetic analysis.
SO - J Virol 2002 Jun;76(12):6185-96
AD - Department of Pediatrics, The University of Texas Health Science Center at San Antonio, 78229, USA.
Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma and several other malignancies. The lack of an efficient infection system has impeded the understanding of KSHV-related pathogenesis. A genetic approach was used to isolate infectious KSHV. Recombinant bacteria artificial chromosome (BAC) KSHV containing hygromycin resistance and green fluorescent protein (GFP) markers was generated by homologous recombination in KSHV-infected BCBL-1 cells. Recombinant KSHV genomes from cell clones that were resistant to hygromycin, expressed GFP, and produced infectious virions after induction with tetradecanoyl phorbol acetate (TPA) were rescued in Escherichia coli and reconstituted in 293 cells. Several 293 cell lines resulting from infection with recombinant virions induced from a full-length recombinant KSHV genome, named BAC36, were obtained. BAC36 virions established stable latent infection in 293 cells, harboring 1 to 2 copies of viral genome per cell and expressing viral latent proteins, with approximately 0.5% of cells undergoing spontaneous lytic replication, which is reminiscent of KSHV infection in Kaposi's sarcoma tumors. TPA treatment induced BAC36-infected 293 cell lines into productive lytic replication, expressing lytic proteins and producing virions that efficiently infected normal 293 cells with a approximately 50% primary infection rate. BAC36 virions were also infectious to HeLa and E6E7-immortalized human endothelial cells. Since BAC36 can be efficiently shuttled between bacteria and mammalian cells, it is useful for KSHV genetic analysis. The feasibility of the system was illustrated through the generation of a KSHV mutant with the vIRF gene deleted. This cellular model is useful for the investigation of KSHV infection and pathogenesis.
UI - 12021355
AU - Fakhari FD; Dittmer DP
TI - Charting latency transcripts in Kaposi's sarcoma-associated herpesvirus by whole-genome real-time quantitative PCR.
SO - J Virol 2002 Jun;76(12):6213-23
AD - Department of Microbiology and Immunology, The University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA.
The division into a latent or lytic life cycle is fundamental to all herpesviridae. In the case of Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus 8), latent genes have been implicated in cell autonomous transformation, while certain lytic genes procure a tumor friendly milieu through paracrine mechanism. To query KSHV transcription, we devised and validated a high-throughput, high-specificity, high-sensitivity, real-time quantitative reverse transcription-PCR array. This novel methodology is applicable to many human pathogens. Its first use demonstrated that the mRNA levels for KSHV LANA, v-cyclin, and v-FLIP do not increase at any time after viral reactivation. The mRNA for LANA-2/vIRF-3 is similarly resistant to viral reactivation. In contrast, every other latent or lytic message was induced. Hence, LANA, v-FLIP, v-cyclin, and LANA-2 constitute a group of uniquely regulated transcripts in the KSHV genome.
UI - 11933267
AU - Jayaram G; Sthaneshwar P
TI - Fine-needle aspiration cytology of phyllodes tumors.
SO - Diagn Cytopathol 2002 Apr;26(4):222-7
AD - Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur. firstname.lastname@example.org
Breast lesions with a significant spindle cell or mesenchymal component are not commonly encountered in fine-needle aspiration (FNA) cytologic material and include a heterologous variety of benign and malignant conditions, with phyllodes tumors (PTs) being the foremost differential diagnostic consideration. This study comprises 28 tumors diagnosed histologically as PT in which FNAC material was available for review. Histological sections and cytological smears from these cases were retrieved and subjected to detailed morphological review. Cytological parameters assessed included ratio of stroma to epithelium, pattern characteristics and cytological characteristics of the stromal, and epithelial components and the background cells. Large and hypercellular stroma fragments, dissociated spindle and plump stromal cells, often accompanied by large, folded sheets of epithelium were cytological features that characterized PT. Smears from malignant PT showed predominantly or solely mesenchymal components. FNAC was a highly reliable procedure for the diagnosis of PT, giving an accuracy rate of 92.8%. Copyright 2002 Wiley-Liss, Inc.
UI - 11933269
AU - Sapi Z; Antal I; Papai Z; Szendroi M; Mayer A; Jakab K; Pajor L; Bodo M
TI - Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques.
SO - Diagn Cytopathol 2002 Apr;26(4):232-42
AD - Department of Oncopathology, Semmelweis University of Health Sciences, Budapest, Hungary. email@example.com
The diagnosis of mesenchymal neoplasm by fine-needle aspiration biopsy (FNAB) has presented a diagnostic challenge. Most reports claim an accuracy approaching 95%, but while they distinguish benign and malignant lesions, the most problematic group, the intermediary malignant group, is omitted. The purpose of this study was to determine whether rapid cytologic diagnosis of soft-tissue tumors could guide surgeons in therapeutic decisions without the need for a tissue biopsy. Ninety-four FNA cytologic specimens were examined by the National Soft Tissue Consortium of Hungary and compared with the corresponding histology. Ordinary lipomas were excluded. Morphologic evaluation was supplemented by ancillary techniques such as fluorescence in situ hybridization (FISH), DNA cytometry, and immunocytochemistry. From a practical clinicopathological point of view, the cases were grouped in the following categories: 1) tumors with definitive diagnosis: a) high-grade malignant neoplasms (high-grade sarcomas, metastatic carcinomas, lymphoma), b) tumors with precise histogenetic origin by cytogenetics, c) benign tumors; 2) tumors of questionable nature. In the first group there were 74 tumors: 22 high-grade sarcomas, six metastatic carcinomas, one malignant lymphoma, 16 malignant tumors in which the precise histogenetic origin could be established by cytogenetic studies, and 29 benign soft-tissue tumors other than lipomas. In the second group there were 20 tumors comprising benign and malignant soft tissue tumors of low grade, wherein the precise nature of the neoplasm could not be established with confidence on cytologic study, even using ancillary techniques. FNAB of soft-tissue tumors combined with ancillary techniques should be considered a viable diagnostic technique for therapeutic protocols. Although the second group is fairly large, we have reliable, well-characterized categories which provide great freedom for preoperative and surgical treatment, thus providing the best chance for healing. Copyright 2002 Wiley-Liss, Inc.
UI - 11866983
AU - He L; Fu L; Wang L; Li P; Lang Z
TI - [A clinicopathological study of clear cell sarcoma of the kidney]
SO - Zhonghua Bing Li Xue Za Zhi 2001 Dec;30(6):422-5
AD - Department of Pathology, Beijing Children's Hospital, Beijing 100045, China.
OBJECTIVE: To study the clinicopathological, immunohistochemical features and the histogenesis of clear cell sarcoma of the kidney (CCSK). METHODS: CCSK specimens from 45 pediatric cases, including 31 male and 14 female with an age range from 3 months to 12 years (mean of 3.2 years), were retrieved. Routine pathological, immunohistochemical and electron microscopic methods were utilized to analyze the CCSK specimens. RESULTS: 35 of the 45 cases were followed from 6 to 192 months. 15 patients presented with bone metastases, 6 had lung or liver metastases, 8 recurred and 20 died. Age and clinical stage at diagnosis correlated with the rate of survival. Histologically, the classic pattern of CCSK consisted of cells with pale cytoplasm, fine nuclear chromatin and indistinct nucleoli separated by an arborizing fibrovascular stroma. Other patterns were identified, including myxoid, spindle, palisading, epithelioid, sclerosing, cellular, cystic, and angiectatic. All tumors contained multiple patterns. Immunohistochemically, all cases were positive for vimentin, but negative for EMA, CK, desmin, actin, S-100, NSE, CD99, CD34 and LCA. Electron microscopy of 9 cases showed features of primitive cell conjunction and few organelles. CONCLUSION: CCSK is a common renal neoplasm of childhood. CCSK may arise from renal mesenchymal cells and has the propensity to metastasize to the bone with poor clinical outcome.
UI - 11866984
AU - Wei Y; Sun M; Zhu H; Xu Z; Wang J; Zhu X
TI - [Detection of SYT-SSX fusion gene in paraffin-embedded tissues and its clinicopathologic significance for synovial sarcoma]
SO - Zhonghua Bing Li Xue Za Zhi 2001 Dec;30(6):426-30
AD - Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.
OBJECTIVE: To investigate the feasibility of detecting SYT-SSX fusion gene in paraffin-embedded tissues and its diagnostic significance for synovial sarcoma (SS). METHODS: Formalin-fixed, paraffin-embedded samples of 38 cases of SS and 40 cases of control tumors (including spindle cell sarcoma and metastatic adenocarcinoma) were retrived from archival materials. SYT-SSX fusion transcripts were detected in all samples by RT-PCR. House-keeping gene Porphobilinogen Deaminase (PBGD) was used to detect the quality of mRNA. RESULTS: PBGD mRNA was detected in 64 of the 78 tumor cases (82.1%). SYT-SSX fusion transcripts was detected in 33 of the 38 synovial sarcoma specimens. No SYT-SSX mRNA expression was found in control tumors. SYT-SSX mRNA expression rate reached 89.2% (33/37) in synovial sarcomas after exclusion of 1 case which was negative for both SYT-SSX and PBGD. In 33 SYT-SSX positive synovial sarcomas, 22 had SYT-SSX1 and 6 had SYT-SSX2 fusion transcripts. In 5 cases, the fusion type could not be distinguished. There was an association between SYT-SSX fusion type and histologic subtype. All 10 biphasic synovial sarcoma cases had the SYT-SSX1 fusion, whereas 12 of 18 monophasic synovial sarcoma had the SYT-SSX1 and 6 had the SYT-SSX2 fusion gene (P < 0.05). CONCLUSIONS: (1) Detection of SYT-SSX fusion gene in paraffin-embedded tissues was found to be a sensitive and specific method for the diagnosis and differential diagnosis of synovial sarcoma. (2) There was an association between SYT-SSX fusion type and histologic subtype.SYT-SSX2 fusion transcript could only be found in monophasic synovial sarcomas.
UI - 11866985
AU - Xu Z; Yang T; Wu B; Zhong H; Yang Z; Zhou B; Zhang C; Zheng J
TI - [Detection and analysis of SYT-SSX fusion gene in synovial sarcoma]
SO - Zhonghua Bing Li Xue Za Zhi 2001 Dec;30(6):431-3
AD - Department of Pathology, Health Science Center, Peking University, Beijing 100083, China.
OBJECTIVE: To demonstrate that a characteristic SYT-SSX fusion gene resulting from chromosomal translocation t (X; 18) (p11; q11) was detectable in archival paraffin-embedded synovial sarcoma tissues. METHODS: SYT-SSX fusion transcripts in 20 synovial sarcomas (histologic subtypes, 15 monophasic and 5 biphasic) were detected and analyzed by the reverse-transcriptase polymerase chain reaction and compared with the results from relevant pathological data. RESULTS: A specific SYT-SSX RT-PCR product was found in 19 of 20 (95%) synovial sarcomas tested and of the 13 tumors containing SYT-SSX2, 10 were monophasic. CONCLUSION: SYT-SSX fusion transcripts are considered as a defining diagnostic marker of synovial sarcomas and the subtypes of SYT-SSX fusion transcripts (SYT-SSX1 and SYT-SSX2) may yield prognostic information.
UI - 11955334
AU - Wang J; Zhu X; Zhang R
TI - [Giant cell fibroblastoma: a clinicopathologic analysis of seven cases]
SO - Zhonghua Bing Li Xue Za Zhi 2002 Feb;31(1):38-41
AD - Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.
OBJECTIVE: To study the clinical, pathological and immunohistochemical features of giant cell fibroblastoma (GCF), with emphasis on its differential diagnosis and histogenesis. METHODS: Seven cases of GCF were investigated by light microscopy and immunohistochemistry. RESULTS: Six cases occurred in children, and one occurred in a 35 year-old adult (mean 9.4 years). Five were male and two were female. Clinically, all cases appeared as slowly growing painless nodules located in the dermis or subcutis of the trunk and extremities. Microscopically, the poorly circumscribed tumor was composed of a proliferation of slightly to moderately atypical spindle cells which were arranged in parallel or wavy fascicles, and embedded in a fibromyxoid to collagenous background. The pathognomonic feature consisted of irregular distributed cleft-like or sinusoid-like pseudovascular spaces lined with a discontinuous layer of pleomorphic spindle cells and multinucleate giant cells. There was transition in shape between these two cells. Immunohistochemially, both cells expressed vimentin and CD34. Follow-up information in five cases showed local recurrences in two cases. CONCLUSIONS: (1) GCF is a distinctive fibroblastic tumor of intermediate malignancy that occurs predominantly in children. Recognizing its clinical and pathological characteristics is important to avoid misdiagnosis with other lesions with similar features. (2) GCF shared clinical, immunohistochemical and cytogenetic features with its adult counterpart-dermatofibrosarcoma protuberans (DFSP). The additional coexistence of GCF and DFSP areas in some primary cases and the reciprocal transformation in recurrent tumors all suggest that they are two closely related entities, possibly representing two members of the CD34 positive dendritic neoplasms.
UI - 12037676
AU - Yang K; Lui WO; Xie Y; Zhang A; Skytting B; Mandahl N; Larsson C;
TI - Larsson O Co-existence of SYT-SSX1 and SYT-SSX2 fusions in synovial sarcomas.
SO - Oncogene 2002 Jun 13;21(26):4181-90
AD - Department of Oncology and Pathology, Karolinska Hospital CCK R8:04, SE-171 76 Stockohlm, Sweden.
The chromosomal translocation t(X;18)(p11.2;q11.2) is tightly linked to the tumorigenesis of synovial sarcoma. Through this translation the SYT gene on chromosome 18 is fused with a testis/cancer antigen gene on the X chromosome, generating either a SYT-SSX1, SYT-SSX2, or less often a SYT-SSX4 fusion gene. It has been anticipated that the individual synovial sarcoma carries only one of these variants, however, in this study we demonstrated that SYT-SSX1 and SYT-SSX2 co-exist in a significant proportion of the cases. From 121 SYT-SSX positive primary tumors, co-expression of SYT-SSX1 and SYT-SSX2 was seen in 12 cases (10%), which were characterized in further detail both at the RNA, DNA and chromosomal level. In all 12 cases the SYT-SSX1 and SYT-SSX2 fusions resulted in identical SYT-SSX fusion transcripts. However, at the genomic level the translocations were different, and most likely occurred between variable intronic sites in the target genes. By interphase FISH analyses of 10 cases SYT-SSX2 translocations were found to be the most abundant in all but one of the cases, in which SYT-SSX1 was predominating. The findings reveal a new heterogenous feature of synovial sarcoma, accounting for approximately 10% of all cases, which may shed light on the molecular genetic mechanisms behind translocations in general, and on the etiology of synovial sarcoma in particular.
UI - 11786394
AU - Masood R; Cesarman E; Smith DL; Gill PS; Flore O
TI - Human herpesvirus-8-transformed endothelial cells have functionally activated vascular endothelial growth factor/vascular endothelial growth factor receptor.
SO - Am J Pathol 2002 Jan;160(1):23-9
AD - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. firstname.lastname@example.org
Kaposi's sarcoma is a vascular tumor commonly associated with human immunodeficiency virus (HIV)-1 and human herpesvirus (HHV-8) also known as Kaposi's sarcoma-associated herpesvirus. The principal features of this tumor are abnormal proliferation of vascular structures lined with spindle-shaped endothelial cells. HHV-8 may transform a subpopulation of endothelial cells in vitro via viral and cellular gene expression. We hypothesized that among the cellular genes, vascular endothelial growth factors (VEGFs) and their cognate receptors may be involved in viral-mediated transformation. We have shown that HHV-8-transformed endothelial cells (EC-HHV-8) express higher levels of VEGF, VEGF-C, VEGF-D, and PlGF in addition to VEGF receptors-1, -2, and -3. Furthermore, antibodies to VEGF receptor-2 inhibited cell proliferation and viability. Similarly, inhibition of VEGF gene expression with antisense oligonucleotides inhibited EC-HHV-8 cell proliferation/viability. The growth and viability of primary endothelial cells and a fibroblast cell line however were unaffected by either the VEGF receptor-2 antibody or the VEGF antisense oligodeoxynucleotides. VEGF and VEGF receptors are thus induced in EC-HHV-8 and participate in the transformation. Inhibitors of VEGF may thus modulate the disease process during development and progression.
UI - 12050510
AU - Chang SS; Cole E; Smith JA Jr; Cookson MS
TI - Pathological findings of gynecologic organs obtained at female radical cystectomy.
SO - J Urol 2002 Jul;168(1):147-9
AD - Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
PURPOSE: Historically anterior pelvic exenteration has been the recommended treatment for invasive urothelial carcinoma in women undergoing radical cystectomy. We evaluated the pathological features of reproductive organs removed during exenteration to determine the incidence of malignant pathology in these organs and the need for removal. MATERIALS AND METHODS: We reviewed the records of all patients Of these 382 patients, we identified 68 females who underwent radical cystectomy for urothelial carcinoma. We reviewed preoperative, operative and pathological findings, including bladder, lymph nodes, uterine and adnexal pathology, in these female patients. RESULTS: Median patient age was 64 years (range 35 to 86). Gynecologic organs were present in 40 of the 68 surgical specimens (59%). The reasons for absent gynecologic pathology were previous hysterectomy in 26 cases and the preservation of organs during orthotopic urinary diversion creation in 2. Malignancy was identified in 3 specimens, including invasive urothelial carcinoma in 2 (5%). In these 2 cases invasion was clearly identified intraoperatively. Low grade stromal sarcoma of the uterus was present in 1 specimen (2%). CONCLUSIONS: In the absence of clinical suspicion radical hysterectomy at cystectomy rarely improves cancer control. Furthermore, secondary malignancies are rare. The functional impact of preserving gynecologic organs is a subject of ongoing study.
UI - 12065559
AU - Hensley ML; Maki R; Venkatraman E; Geller G; Lovegren M; Aghajanian C;
TI - Sabbatini P; Tong W; Barakat R; Spriggs DR Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial.
SO - J Clin Oncol 2002 Jun 15;20(12):2824-31
AD - Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
PURPOSE: Few chemotherapy agents are active in leiomyosarcoma (LMS), particularly LMS that has progressed after doxorubicin treatment. We sought to determine the response to gemcitabine plus docetaxel among patients with LMS. PATIENTS AND METHODS: Patients with unresectable LMS of uterine (n = 29) or other (n = 5) primary sites who did not respond to zero to two prior chemotherapy regimens were enrolled onto a phase II study of gemcitabine 900 mg/m(2) intravenously (i.v.) on days 1 and 8 plus docetaxel 100 mg/m(2) i.v. on day 8 with granulocyte colony-stimulating factor given subcutaneously on days 9 to 15, delivered every 21 days. Patients with prior pelvic radiation received 25% lower doses of both agents. Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2 and by 90-minute infusion in all subsequent cycles. Pharmacokinetic studies assessed in vivo differences in gemcitabine concentrations with different rates of infusion. RESULTS: Thirty-four patients (median age, 55 years; range, 32 to 74 years) have enrolled. Fourteen had received prior pelvic radiation. Sixteen of 34 patients had progressed after doxorubicin-based therapy; 18 had no prior chemotherapy. Among 34 patients, complete response was observed in three patients and partial response in 15, for an overall response rate of 53% (95% confidence interval, 35% to 70%). Seven patients had stable disease. Fifty percent of patients previously treated with doxorubicin responded. Hematologic toxicity was common (neutropenia: grade 3, 15%; grade 4, 6%; thrombocytopenia: grade 3, 26%; grade 4, 3%), but neutropenic fever (6%) and bleeding events (0%) were rare. The median time to progression was 5.6 months (range, 4 to 10 months). CONCLUSION: Gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with LMS.
UI - 10679647
AU - Fioretti F; Tavani A; Gallus S; Negri E; Franceschi S; La Vecchia C
TI - Menstrual and reproductive factors and risk of soft tissue sarcomas.
SO - Cancer 2000 Feb 15;88(4):786-9
AD - Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.
BACKGROUND: Soft tissue sarcomas (STS) are a heterogeneous group of neoplasms whose etiology remains largely undefined. A role for female hormones in the development of STS has been suggested. To investigate this possibility, the authors analyzed data from a hospital-based case-control study conducted in Northern Italy between 1983 and 1998. METHODS: Cases were 104 women aged < 79 years with incident STS who were admitted to the cancer institutes and major teaching and general hospitals. Controls were 505 women admitted to the same network of hospitals for acute, nonneoplastic, nongynecologic, and nonimmune-related conditions. RESULTS: The multivariate odds ratio (OR) for women aged >/= 15 years compared with those aged < 12 years at menarche was 1.94 (95% confidence intervals [95% CI], 0.80-4.74). No association with STS risk was observed for menstrual cycle pattern, age at menopause, parity, and abortions. Late age at first pregnancy and birth were found to be related to an increased risk of STS, with an OR of 3.16 (95% CI, 0. 96-10.44) and 2.79 (95%% CI, 0.79-9.90) for women aged >/= 30 years at first pregnancy and birth compared with those aged < 20 years. The trend in risk was significant for age at first pregnancy. No relation with the risk of STS emerged for age at last birth and time since first or last birth. CONCLUSIONS: The risk of STS was found to be weakly related to late age at first pregnancy or birth, but not to other menstrual and reproductive factors. Copyright 2000 American Cancer Society.
UI - 11827409
AU - Scolyer RA; McKenzie PR; Achmed D; Lee CS
TI - Can phyllodes tumours of the breast be distinguished from fibroadenomas using fine needle aspiration cytology?
SO - Pathology 2001 Nov;33(4):437-43
AD - Department of Anatomical Pathology and the Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. email@example.com
In an attempt to determine whether it is possible to distinguish phyllodes tumours (PTs) of the breast from fibroadenomas (FAs) using fine needle aspiration cytology (FNAC), we reviewed the cytological slides of eight histopathologically confirmed PTs (six benign and two malignant) and compared them with cytological features of 13 histopathologically confirmed FAs. Each author independently, "blindly" assessed architectural and cytological features of the stromal (six features) and epithelial (seven features) components and the cytological background (three features) and gave a favoured diagnosis for each case. Four of six benign PTs, one of two malignant PTs and 11 of 13 FAs were correctly diagnosed cytopathologically by at least three of the authors. The presence of hypercellular stromal fragments was the most useful feature in distinguishing PTs from FAs, and the presence of cytological atypia of the stromal cells was the most important feature in distinguishing malignant from benign PTs. Sampling error was the most common reason for cytological misdiagnosis of PTs. The two FAs misdiagnosed as PTs were each of cellular type. The results of this study suggest that it is possible to distinguish PTs from FAs using FNAC in most cases. We recommend that if hypercellular stromal fragments are identified in a FNAC specimen of a fibroepithelial lesion, the cytopathologist should raise the possibility of a PT and the surgeon treat the patient accordingly.
UI - 12087954
AU - Dechev IY; Banchev AB; Kadim MN; Zdravchev SA
TI - Penile cancer--surgical treatment of the primary tumor.
SO - Folia Med (Plovdiv) 2001;43(4):46-50
AD - Medical University, Department of Urology, 15A Vassil Aprilov St., 4000 Plovdiv, Bulgaria.
OBJECTIVE: To present our experience in the surgical treatment of primary tumor in penile cancer based on the accepted oncologic principles and indications for the existing surgical methods of treatment. MATERIAL AND METHODS: A retrospective analysis of 54 patients with histologically proven malignant penile cancer treated surgically at the Urology department of MHAT "St George", Plovdiv between 1975 and performed. Penile amputations were significantly more than penile-preserving operations. DISCUSSION: Differentiation and tumor stage are paramount in the choice of surgical strategy for penile cancer.
UI - 11870247
AU - Savage DG; Antman KH
TI - Imatinib mesylate--a new oral targeted therapy.
SO - N Engl J Med 2002 Feb 28;346(9):683-93
AD - Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
UI - 12042982
AU - Issels RD; Schlemmer M
TI - Current trials and new aspects in soft tissue sarcoma of adults.
SO - Cancer Chemother Pharmacol 2002 May;49 Suppl 1():S4-8
AD - Department of Internal Medicine III, Klinikum Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany. Issels@med3.med.uni-muenchen.de
PURPOSE: For high-risk soft tissue sarcoma (HR-STS) of adults new treatment strategies are needed to improve outcome with regard to local control and overall survival. Therefore, systemic chemotherapy has been integrated either after (adjuvant) or before (neoadjuvant) optimal local treatment by surgery and radiotherapy in HR-STS. METHODS AND RESULTS: The Soft Tissue and Bone Sarcoma Group (STBSG) of the European Organization for Research and Treatment of Cancer (EORTC) is conducting an open randomized trial of adjuvant chemotherapy in high-grade primary or recurrent STS at any site (EORTC 62931). In all cases primary surgery should be curative in intent. All eligible patients are randomized after completion of definitive surgery to receive either radiotherapy alone with no further treatment (observation arm) or five cycles of doxorubicin (70 mg/m(2)) plus ifosfamide (5 g/m(2)) using G-CSF to support dose intensity followed by radiotherapy (chemotherapy arm). This more aggressive chemotherapy regimen within an adjuvant setting might retain sufficient antitumor activity to convert response rates into survival benefit. At present more than 220 patients have been recruited for this trial. To explain the rationale for the EORTC 62931 protocol, reported results of other clinical adjuvant protocols including a meta-analysis are given. In close collaboration with the European Society of Hyperthermic Oncology (ESHO) the STBSG has also initiated a randomized trial of neoadjuvant chemotherapy in primary or recurrent HR-STS as an EORTC Intergroup study. According to the inclusion criteria as defined (tumor size >or=5 cm + grade II or III + deep location + extracompartmental extension) for the EORTC 62961/ESHO RHT-95 Intergroup study, the majority of patients with HR-STS recruited for this pre- and postoperative multimodality treatment protocol cannot be cured by standard procedures. All eligible patients are randomized to receive either four cycles of EIA (etoposide 250 mg/m(2) + ifosfamide 6 g/m(2) + doxorubicin 50 mg/m(2)) within 12 weeks (chemotherapy arm) or the same EIA regimen combined with regional hyperthermia (RHT + chemotherapy arm). The patients then receive optimal local treatment using adequate surgery immediately followed by radiotherapy. Thereafter an additional four cycles of EIA chemotherapy are given with or without RHT according to the initial randomization. At present more than 150 patients have been recruited for this trial. The integration of RHT as a new potent treatment modality if combined with EIA chemotherapy as first-line treatment for well-defined risk groups is based upon encouraging long-term results of phase II studies both in pretreated patients with HR-STS and in those with locally advanced disease. CONCLUSIONS: In summary, significant prognostic variables recognized for patients with STS have been addressed in the design of two open phase III clinical trials on adjuvant and neoadjuvant chemotherapy. The best chance for offering such treatment strategies following evidence-based medicine criteria to eligible patients with HR-STS depends upon early contact with the coordinator of the individual protocol prior to any treatment.
UI - 12063389
AU - Roberts I; Gordon A; Wang R; Pritchard-Jones K; Shipley J; Coleman N
TI - Molecular cytogenetic analysis consistently identifies translocations involving chromosomes 1, 2 and 15 in five embryonal rhabdomyosarcoma cell lines and a PAX-FOXO1A fusion gene negative alveolar rhabdomyosarcoma cell line.
SO - Cytogenet Cell Genet 2001;95(3-4):134-42
AD - Hutchison/MRC Research Centre, Cambridge, UK. firstname.lastname@example.org
Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays skeletal muscle differentiation. Two main histological variants are recognised, alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent chromosome translocations characteristic of ARMS have been reported, no such cytogenetic abnormality has yet been described in ERMS. We have used multiple colour chromosome painting to obtain composite karyotypes for five ERMS cell lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ hybridisation (M-FISH) using series of seven colour paint sets generated to examine specific abnormalities, and comparative genomic hybridisation (CGH). This approach enabled us to obtain karyotypes of the cell lines in greater detail than previously possible. Several recurring cytogenetic abnormalities were demonstrated, including translocations involving chromosomes 1 and 15 and chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1 and 15 have previously been recorded in two primary cases of ERMS by conventional cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of ERMS tumourigenesis and may enable the development of novel approaches to the clinical management of this tumour. Copyright 2002 S. Karger AG, Basel
UI - 12079023
AU - Ozaki T; Putzke M; Burger H; Gosheger G; Winkelmann W; Lindner N
TI - Infiltration of sarcomas into the hip joint: comparison of CT, MRI and histologic findings in 67 cases.
SO - Acta Orthop Scand 2002 Apr;73(2):220-6
AD - Department of Orthopaedics, Westfalische Wilhelms-University, Munster, Germany. email@example.com
We analyzed the incidence, route, and characteristics of hip joint infiltration in pelvic or proximal femoral sarcomas. 67 patients with a sarcoma that originated around the hip joint (50 pelvic and 17 femoral) were included in this study. Preoperative CT and MRI were matched with the histological findings in tumor specimens. Tumor infiltration into the hip joint was suspected on the basis of preoperative imaging in 29 patients due to articular cartilage disruption, diffuse signal changes in the acetabulum or femoral neck, signs of a tumor in the joint, or markedjoint effusion. Of these 29 patients, 15 showed tumor invasion on histological examination. 12 of 31 chondrosarcomas, none of 12 Ewing's sarcomas, and 3 of 24 osteosarcomas infiltrated into the hip joint (p = 0.008). 10 of 26 low-grade sarcomas and 5 of 41 high-grade sarcomas infiltrated into the hip joint (p = 0.02). The joint infiltration rate of the chondrosarcomas was related to their size. Of 10 tumors originating in the acetabulum, 9 penetrated through or around the osseous-ligamentous junction and one through the acetabular cartilage. In 5 proximal femur lesions, all infiltrated the joint through the femoral neck, 3 of them also through the ligamentum teres.
UI - 11731909
AU - Nagase H; Ikeda K; Sakai Y
TI - Inhibitory effect of magnolol and honokiol from Magnolia obovata on human fibrosarcoma HT-1080. Invasiveness in vitro.
SO - Planta Med 2001 Nov;67(8):705-8
AD - Department of Hygienics, Gifu Pharmaceutical University, Gifu, Japan. firstname.lastname@example.org
We investigated the inhibitory effect of Magnolia obovata Thunb. bark ethanol extracts on human fibrosarcoma HT-1080 cells invasion in a reconstituted basement membrane [Matrigel (MG)]. We found that the effective components of the bark ethanol extracts were magnolol and honokiol, two biphenyl compounds. The extracts, magnolol and honokiol, did not affect HT-1080 cells adhesion to MG, but did inhibit HT-1080 cells migration at a high concentration (100 microM). HT-1080 cells secrete matrix metalloproteinase (MMP)-9, which degrades the extracellular matrix as a part of the invasive process. Magnolol and honokiol inhibited the activity of MMP-9, which may have been responsible, in part, for the inhibition of tumor cell invasiveness.
UI - 11984496
AU - Noel G; Mammar H; Ferrand R; Desblancs C; Nauraye C; Mazeron JJ
TI - [ANOCEF MEETING December 8, 2001. Summary of the meeting]
SO - Rev Neurol (Paris) 2002 Apr;158(4):497-509
AD - Centre de protontherapie d'Orsay, Orsay, France.
UI - 12036902
AU - Fritz B; Schubert F; Wrobel G; Schwaenen C; Wessendorf S; Nessling M;
TI - Korz C; Rieker RJ; Montgomery K; Kucherlapati R; Mechtersheimer G; Eils R; Joos S; Lichter P Microarray-based copy number and expression profiling in dedifferentiated and pleomorphic liposarcoma.
SO - Cancer Res 2002 Jun 1;62(11):2993-8
AD - Deutsches Krebsforschungszentrum, Abteilung Molekulare Genetik (H0700), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Sixteen dedifferentiated and pleomorphic liposarcomas were analyzed by comparative genomic hybridization (CGH) to genomic microarrays (matrix-CGH), cDNA-derived microarrays for expression profiling, and by quantitative PCR. Matrix-CGH revealed copy number gains of numerous oncogenes, i.e., CCND1, MDM2, GLI, CDK4, MYB, ESR1, and AIB1, several of which correlate with a high level of transcripts from the respective gene. In addition, a number of genes were found differentially expressed in dedifferentiated and pleomorphic liposarcomas. Application of dedicated clustering algorithms revealed that both tumor subtypes are clearly separated by the genomic profiles but only with a lesser power by the expression profiles. Using a support vector machine, a subset of five clones was identified as "class discriminators." Thus, for the distinction of these types of liposarcomas, genomic profiling appears to be more advantageous than RNA expression analysis.
UI - 12103287
AU - O'Sullivan B; Davis AM; Turcotte R; Bell R; Catton C; Chabot P; Wunder
TI - J; Kandel R; Goddard K; Sadura A; Pater J; Zee B Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.
SO - Lancet 2002 Jun 29;359(9325):2235-41
AD - Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada. email@example.com
BACKGROUND: External-beam radiotherapy (delivered either preoperatively or postoperatively) is frequently used in local management of sarcomas in the soft tissue of limbs, but the two approaches differ substantially in their potential toxic effects. We aimed to determine whether the timing of external-beam radiotherapy affected the number of wound healing complications in soft-tissue sarcoma in the limbs of adults. METHODS: After stratification by tumour size (< or = 10 cm or >10 cm), we randomly allocated 94 patients to preoperative radiotherapy (50 Gy in 25 fractions) and 96 to postoperative radiotherapy (66 Gy in 33 fractions). The primary endpoint was rate of wound complications within 120 days of surgery. Analyses were per protocol for primary outcomes and by intention to treat for secondary outcomes. FINDINGS: Median follow-up was 3.3 years (range 0.27-5.6). Four patients, all in the preoperative group, did not undergo protocol surgery and were not evaluable for the primary outcome. Of those patients who were eligible and evaluable, wound complications were recorded in 31 (35%) of 88 in the preoperative group and 16 (17%) of 94 in the postoperative group (difference 18% [95% CI 5-30], p=0.01). Tumour size and anatomical site were also significant risk factors in multivariate analysis. Overall survival was slightly better in patients who had preoperative radiotherapy than in those who had postoperative treatment (p=0.0481). INTERPRETATION: Because preoperative radiotherapy is associated with a greater risk of wound complications than postoperative radiotherapy, the choice of regimen for patients with soft-tissue sarcoma should take into account the timing of surgery and radiotherapy, and the size and anatomical site of the tumour.
UI - 11986186
AU - Jones JJ; Catton CN; O'Sullivan B; Couture J; Heisler RL; Kandel RA;
TI - Swallow CJ Initial results of a trial of preoperative external-beam radiation therapy and postoperative brachytherapy for retroperitoneal sarcoma.
SO - Ann Surg Oncol 2002 May;9(4):346-54
AD - University of Toronto Sarcoma Group, Princess Margaret Hospital, Toronto, Ontario, Canada.
BACKGROUND: Surgical resection alone does not cure the majority of patients with retroperitoneal sarcoma (RPS). We evaluated the effects of preoperative external-beam radiotherapy (XRT) and postoperative brachytherapy (BT) combined with complete surgical resection. METHODS: Fifty-five patients with primary or locally recurrent RPS judged to be resectable were entered onto a trial of combined therapy and observed prospectively. Forty-six patients underwent complete gross resection with curative intent. Of these, 41 patients completed preoperative XRT and 23 patients received BT. Outcome measures were treatment toxicity, overall survival, and disease-free survival (DFS). RESULTS: Preoperative XRT was very well tolerated and was associated with Radiation Therapy Oncology Group acute toxicity scores of < or = 2 in all patients. Acute postoperative and BT-related toxicity resulted in modified RTOG scores of > or = 3 in 39.1% (18 of 46) of patients. Late toxicity was associated with death in 4.3% (2 of 46) and with life-threatening illness in 2.2% (1 of 46) of patients, all of whom had been treated with BT to the upper abdomen. The 2-year overall survival and DFS for resected RPS were 88% and 80%, respectively. Significantly better 2-year DFS was achieved in patients with primary RPS and in those with low-grade tumors (93% and 95%, respectively). CONCLUSIONS: The initial results of combined therapy are promising. Although preoperative XRT was very well tolerated, BT to the upper abdomen was associated with substantial toxicity. Our current protocol includes selective application of BT to the lower abdomen only.
UI - 11986187
AU - van Ginkel RJ; Limburg PC; Piers DA; Koops HS; Hoekstra HJ
TI - Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan.
SO - Ann Surg Oncol 2002 May;9(4):355-63
AD - Department of Surgical Oncology, Groningen University Hospital, Groningen, The Netherlands.
BACKGROUND: The aim of this study was to analyze the value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in patients treated with hyperthermic isolated limb perfusion with tumor necrosis factor-alpha (TNF alpha) and melphalan. METHODS: Forty-eight patients with melanoma (n = 14) or soft tissue sarcoma (n = 34) of an extremity underwent 51 perfusions. Perfusion was performed at the iliac level in 22 cases, at the popliteal level in 16 cases, at the femoral level in 7 cases, and at the axillary level in 6 cases. Leakage rates and perfusion circuit and systemic levels of TNF alpha, interleukin-6, and C-reactive protein were determined, as were systemic hematological and metabolic profiles and tumor response. RESULTS: The mean isotopically measured leakage was 2.9%. Systemic leakage was < or = 2% in 28 perfusions and >2% in 23 perfusions. The correlation between the maximal monitored leakage and maximal systemic TNF alpha levels was.7114. The area under the curve for TNF alpha in the perfusion circuit, indicating the exposure of the perfused limb to TNF alpha, was 18.7% lower in the >2% leakage group. No significant differences in tumor response were found between groups. The area under the curve for systemic TNF alpha, indicating the exposure of the patient to TNF alpha, was 18.1 times higher in the >2% leakage group, resulting in a significant decrease in leukocyte and platelet count, hyperbilirubinemia, hypocholesterolemia, and proteinemia. No beneficial effect of the systemically leaked TNF and melphalan was seen on the occurrence of distant metastasis during follow-up. There was a significant difference between perfusions performed at the iliac and femoral levels compared with leakage values at the popliteal level. CONCLUSIONS: A good correlation between RISA leakage measurement and TNF alpha exposure during and after hyperthermic isolated limb perfusion with TNF alpha and melphalan was demonstrated. RISA leakage measurement serves as a good guide for the effectiveness of isolation during perfusion. If leakage exceeds the 2% limit during perfusion, less exposure of the tumor-bearing limb to TNF alpha, increased exposure of the patient systemic circulation to TNF alpha, and more systemic side effects can be expected.
UI - 12079962
AU - Liu S; Wang Z; Chen AQ; Zhou GH; Jiang ZB; Xiao MD
TI - Cardiac myxoma and myxosarcoma: clinical experience and immunohistochemistry.
SO - Asian Cardiovasc Thorac Ann 2002 Mar;10(1):8-11
AD - Department of Cardiovascular Surgery, Shanghai First People's Hospital, Shanghai, People's Republic of China. firstname.lastname@example.org females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.