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Abramson Cancer CenterNCI CANCERLIT® Search: Soft Tissue Sarcoma/Rhabdomyosarcoma - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11764658
AU - De Neve W; Claus F; Duthoy W; De Meerleer G; De Wagter C
TI -
Intensity modulation techniques for improvement of normal tissue
tolerance.
SO - Front Radiat Ther Oncol 2002;37():163-73
AD - Division of Radiotherapy, Ghent University Hospital, Ghent, Belgium.
wilfried@krtkgl.rug.ac.be
2
UI - 11867783
AU - Koyama T; Fletcher JG; Johnson CD; Kuo MS; Notohara K; Burgart LJ
TI -
Primary hepatic angiosarcoma: findings at CT and MR imaging.
SO - Radiology 2002 Mar;222(3):667-73
AD - Department of Diagnostic Imaging and Nuclear Medicine, School of
Medicine, Kyoto University, Japan.
PURPOSE: To evaluate and describe cross-sectional imaging findings in
patients with pathologically confirmed primary hepatic angiosarcoma.
MATERIALS AND METHODS: Findings from imaging examinations in 13 patients
with pathologically confirmed primary hepatic angiosarcoma were
retrospectively reviewed (computed tomographic [CT] images obtained in
10 patients and magnetic resonance [MR] images obtained in five patients
were available for review). Two gastrointestinal radiologists evaluated
lesion number, size, attenuation and signal intensity characteristics,
and the pattern and degree of contrast material enhancement. Medical
records were reviewed for clinical features associated with
angiosarcoma. RESULTS: Angiosarcoma appeared as multiple nodules (n =
6), as dominant masses (n = 6), or as a diffusely infiltrating lesion (n
= 1). Multiple nodules were hypoattenuating at unenhanced and contrast
material--enhanced CT (six of six patients). When dominant masses were
encountered at MR imaging, T2-weighted MR imaging demonstrated
heterogeneous internal architecture (four of four patients) similar to
that of hepatocellular carcinoma. Multiphase contrast-enhanced CT and MR
images showed dominant masses to have heterogeneous and progressive
enhancement (three of three patients). Clinical features associated with
angiosarcoma included splenic metastases (six of 13 patients),
thrombocytopenia (seven of 13 patients), disseminated intravascular
coagulation (four of 13 patients), and hemolytic anemia (three of 13
patients). CONCLUSION: Primary hepatic angiosarcoma exhibits a spectrum
of appearances that reflect its varied pathologic features.
3
UI - 11867201
AU - Dan'ura T; Kawai A; Morimoto Y; Naito N; Yoshida A; Inoue H
TI -
Apoptosis and expression of its regulatory proteins in soft tissue
sarcomas.
SO - Cancer Lett 2002 Apr 25;178(2):167-74
AD - Department of Orthopaedic Surgery, Faculty of Medicine, Okayama
University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Information for the occurrence and extent of apoptosis in soft tissue
sarcoma (STS) and their clinical implication are limited. In 102 cases
of STSs, apoptosis was detected by terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling method and expression of
Bcl-2, Bax, MIB-1 and p53 protein was examined immunohistochemically.
The apoptotic index of the STSs ranged from 0 to 15% with an average
value of 1.9%. The mean values of positive cell staining for Bcl-2, Bax,
MIB-1 and p53 protein were 32.1, 40.8, 17.0 and 20.3%, respectively. The
extent of apoptosis and expression of Bcl-2 protein were correlated to
the histologic types of the tumor. Synovial sarcoma had a significantly
higher expression of Bcl-2 protein, and lower incidence of apoptosis.
STS underwent apoptosis at a constitutional level. There were no
significant relationships between extent of the apoptosis, expression of
its regulatory proteins and prognosis of the patients.
4
UI - 11920169
AU - Agbalika F; Marolleau JP; Brouet JC
TI -
Interleukin-6 stimulates HHV-8 replication in bone marrow cultures and
infected cell lines.
SO - Hematol J 2000;1(1):48-52
AD - Laboratory of Virology, Hopital Saint-Louis, Paris, France.
INTRODUCTION: The significance of HHV-8 DNA detection in bone marrow
stromal cells from patients with multiple myeloma is still
controversial. Since IL-6 plays a key role in the pathogenesis of
myeloma, we studied the effect of this lymphokine on HHV-8 DNA
detection. MATERIALS AND METHODS: Amplification of HHV-8 DNA from
long-term bone marrow cultures established from normal individuals in
the presence or absence of 1 ng/ml IL-6 and from an HHV-8 infected ISI
cell line. RESULTS AND CONCLUSIONS: IL-6 increased HHV-8 replication in
seven of ten bone marrow cultures as well as in the ISI cell line.
Quantitative PCR showed a 3-100-fold increase in HHV-8 DNA copy
number/microg DNA. These data suggest that when IL-6 is present in the
micro-environment, HHV-8 replicates and may be amplified in the absence
of systemic infection in patients without cellular immune deficiency.
5
UI - 11884051
AU - Stefanovski PD; Bidoli E; De Paoli A; Buonadonna A; Boz G; Libra M;
TI -
Morassut S; Rossi C; Carbone A; Frustaci S
Prognostic factors in soft tissue sarcomas: a study of 395 patients.
SO - Eur J Surg Oncol 2002 Mar;28(2):153-64
AD - Division of Medical Oncology, Centro di Riferimento Oncologico, Aviano,
Italy.
AIMS: The aim of this study was to report prognostic factors, end-points
of local recurrence, distant recurrence, post-metastasis survival, and
overall survival in a cohort of patients with soft tissue sarcomas.
METHODS: We analysed a database of 395 patients affected by primary soft
tissue sarcomas of various primary sites, treated and followed up at the
metastasis, age, sex, performance status, and haemoglobin value were
significant for overall survival. Histology, grade, stage, and surgical
margins were significant for local recurrence. Grade, size, and stage,
were significant for distant recurrence; and surgical margin was
significant variable for post-metastasis survival. CONCLUSIONS: Grade,
size, and TNM stage (UICC/AJCC) have stronger prognostic significance
for overall survival and distant recurrence than for local relapse.
Positive surgical margins are the main predictors for local relapse. Age
was the most consistent adverse independent prognostic factor for
survival. Copyright Harcourt Publishers Limited.
6
UI - 11846301
AU - Breitfeld PP; Lyden E; Raney RB; Teot LA; Wharam M; Lobe T; Crist WM;
TI -
Maurer HM; Donaldson SS; Ruymann FB
Ifosfamide and etoposide are superior to vincristine and melphalan for
pediatric metastatic rhabdomyosarcoma when administered with irradiation
and combination chemotherapy: a report from the Intergroup
Rhabdomyosarcoma Study Group.
SO - J Pediatr Hematol Oncol 2001 May;23(4):225-33
AD - Intergroup Rhabdomyosarcoma Study Group, Children's Cancer Group,
Arcadia, California, USA. breit003@mc.duke.edu
PURPOSE: This study was designed to estimate the partial and complete
response rates (CR and PR) of two novel drug pairs (vincristine and
melphalan vs. ifosfamide and etoposide) and to improve overall survival
of previously untreated patients with metastatic rhabdomyosarcoma.
PATIENTS AND METHODS: One hundred twenty-eight patients were randomly
assigned to phase II window therapy consisting of vincristine and
melphalan (VM-containing regimen) or ifosfamide and etoposide
(IE-containing regimen). Brief window therapy (12 wks) was immediately
followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC),
chemotherapy, surgery, and irradiation, with continuation of either VM
or IE in patients with initial response. Major endpoints were initial CR
and PR rates after the phase II window phase of therapy, failure-free
survival (FFS), and survival. RESULTS: Patients who received the
VM-containing regimen experienced significantly more anemia,
neutropenia, thrombocytopenia, and had more cyclophosphamide dose
reductions. The initial PR and CR rates were not significantly different
for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428).
However, FFS and overall survival (OS) at 3 years were significantly
better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS:
55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen
produced a high response rate, inclusion of melphalan appeared to limit
the cyclophosphamide dose that could be administered, and ultimately,
this regimen was associated with a significantly worse outcome than was
the IE-containing regimen. Also, the IE-containing regimen was
associated with a gratifyingly high survival rate at 3 years (55%),
which is significantly higher than has been observed on any previous
Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We
believe that this promising outcome indicates that this drug pair merits
further randomized testing in metastatic rhabdomyosarcoma.
7
UI - 11925138
AU - Amant F; de la Rey M; Dorfling CM; van der Walt L; Dreyer G; Dreyer L;
TI -
Vergote I; Lindeque BG; Van Rensburg EJ
PTEN mutations in uterine sarcomas.
SO - Gynecol Oncol 2002 Apr;85(1):165-9
AD - Division of Gynecological Oncology, Department of Obstetrics and
Gynecology, UZ Gasthuisberg, Leuven, Belgium.
Frederic.Amant@uz.kuleuven.ac.be
OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas,
leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are
highly aggressive neoplasms with a biphasic histology of carcinomatous
and sarcomatous elements. It is now generally accepted that
carcinosarcomas are biphasic tumors that have to be regarded as
endometrial carcinomas where metaplasia occurs. Mutations of the PTEN
tumor suppressor gene, located on 10q23, play a significant role in the
pathogenesis of the endometrioid type of endometrial carcinoma. Loss of
heterozygosity of chromosome 10q has been reported in uterine
leiomyosarcoma. Since little is known about the molecular pathobiology,
our goal was to investigate the potential role of the PTEN gene in the
carcinogenesis of uterine sarcomas. METHODS: We examined 21
carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas
using exon-by-exon polymerase chain reaction-single-strand conformation
polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas
were found to harbor somatic PTEN mutations. Of these, approximately 17%
(3/18) were carcinosarcomas with endometrioid-type carcinoma components
and approximately 5% (1/21) were leiomyosarcomas. No mutations were
detected in carcinosarcomas with nonendometrioid carcinoma components
(0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data
suggest that intragenic PTEN mutations are involved in the genesis of
uterine carcinosarcomas with endometrioid-type carcinoma components but
rarely contribute to the pathobiology of uterine leiomyosarcomas.
8
UI - 11925150
AU - Moore RG; Steinhoff MM; Granai CO; DeMars LR
TI -
Vulvar epithelioid sarcoma in pregnancy.
SO - Gynecol Oncol 2002 Apr;85(1):218-22
AD - Department of Obstetrics and Gynecology, Program in Women's Oncology,
Brown University, Providence, Rhode Island 02905, USA. rmoore@wihri.org
BACKGROUND: Epithelioid sarcoma is a soft tissue tumor rarely found
centrally and even less commonly on the vulva. Vulvar sarcoma in
pregnancy is also exceedingly rare with only five cases reported to
date, none of which have been an epithelioid sarcoma. CASE: We report a
case of a 29-year-old woman presenting with a vulvar epithelioid sarcoma
at 36 weeks of gestation. The patient underwent a radical resection 6
weeks postpartum followed by chemotherapy. Despite a radical
hemivulvectomy and doxorubicin and ifosfamide chemotherapy, she
developed pulmonary metastasis and died of tumor-related pulmonary
failure secondary to her disease 612 months after diagnosis. To our
knowledge this is the first case of a vulvar epithelioid sarcoma
presenting during pregnancy. The English literature is reviewed and a
total of 18 previous cases of vulvar epithelioid sarcoma have been
reported outside of pregnancy. Insight into the biological behavior and
therapeutic management of this disease is discussed. CONCLUSION: The
optimal management of vulvar epithelioid sarcoma remains to be
determined. However, it would seem that early and aggressive surgical
resection provides the best possibility for cure. The role of radiation
and/or chemotherapy remains to be determined.
9
UI - 11859200
AU - Martin SA; Sears DL; Sebo TJ; Lohse CM; Cheville JC
TI -
Smooth muscle neoplasms of the urinary bladder: a clinicopathologic
comparison of leiomyoma and leiomyosarcoma.
SO - Am J Surg Pathol 2002 Mar;26(3):292-300
AD - Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester,
Minnesota 55905, USA.
We report the clinicopathologic, immunohistochemical, and DNA ploidy
findings of 18 leiomyosarcomas of the urinary bladder. In addition, we
compare these malignant smooth muscle tumors with 10 cases of urinary
bladder leiomyoma. The 14 male and four female patients with
leiomyosarcoma ranged in age from 25 to 88 years (mean 64 years). The
tumors ranged from 3.0 to 15.0 cm (mean 7.1 cm) in greatest dimension
and were moderately to highly cellular, consisting of interlacing
fascicles of spindled cells with mild to marked nuclear atypia.
Coagulative tumor necrosis was identified in 14 cases (78%), and mitotic
activity ranged from 1 to 42 mitotic figures (MF) per 10 high power
fields (HPF) (mean 12 MF/10 HPF). Tumors were classified as either
high-grade (12 cases) or low-grade (six cases) based on nuclear atypia,
mitotic activity, and tumor necrosis. Actin positivity was present in 15
tumors (83%), and desmin immunoreactivity was present in seven tumors
(39%). All cases were negative for epithelial markers and S-100.
Proliferative activity, as assessed by MIB-1 staining, ranged from 0.1%
to 51.4% (median 9.1%). Seven (39%) of the leiomyosarcomas were DNA
aneuploid, eight (44%) were tetraploid, and three (17%) were diploid.
Five patients underwent radical cystoprostatectomy, one radical
cystectomy, seven had partial cystectomy, two underwent pelvic
exenteration, and three patients had transurethral resection only.
Follow-up information was available on all 18 cases and ranged from 2 to
68 months (mean 22 months). Of the 12 patients with high-grade tumors,
six (50%) died of disease from 2 to 20 months (mean 7 months) after
diagnosis and three patients (25%) are alive with metastatic tumor. Two
of the six patients with low-grade leiomyosarcoma died of tumor, 61 and
68 months after diagnosis. There were five male and five female patients
with leiomyoma ranging in age from 22 to 78 years (mean 61 years). The
tumors ranged from 0.5 to 4.5 cm (mean 1.6 cm) in greatest dimension,
were well circumscribed, and had low cellularity. Mitotic activity,
necrosis, and cellular atypia were absent, and the tumors were strongly
positive for both actin and desmin. MIB-1 staining ranged from 0% to
3.8% (median 0.8%). Seven (87.5%) of the leiomyomas were DNA diploid or
near-diploid and one (12.5%) was DNA aneuploid. Six patients were
treated with transurethral resection and four with partial cystectomy.
All 10 patients were alive at the last follow-up (mean follow-up 75
months), and no tumor recurred or metastasized. Our study shows that
low-grade leiomyosarcomas are capable of malignant behavior, and
high-grade leiomyosarcomas appear to behave more aggressively than
low-grade tumors. In addition, the diagnosis of urinary bladder
leiomyoma should be reserved for noninfiltrative smooth muscle tumors
lacking mitotic activity, cytologic atypia, and necrosis.
10
UI - 11981942
AU - Watanabe K
TI -
Leiomyosarcoma versus myofibrosarcoma.
SO - Am J Surg Pathol 2002 Mar;26(3):393-4; discussion 394-6
11
UI - 11900566
AU - Laskin WB; Miettinen M
TI -
Epithelial-type and neural-type cadherin expression in malignant
noncarcinomatous neoplasms with epithelioid features that involve the
soft tissues.
SO - Arch Pathol Lab Med 2002 Apr;126(4):425-31
AD - Department of Pathology, Northwestern University Medical School,
Chicago, IL 60611-3053, USA. wbl769@northwestern.edu
CONTEXT: Transmembrane adhesion molecules, epithelial-type cadherin
(ECAD) and neural-type cadherin (NCAD), help in regulating
transformations between epithelial and mesenchymal cells in the
developing embryo and in maintaining the epithelioid phenotype.
Consequently, the presence of epithelioid cells in certain malignant
noncarcinomatous neoplasms raises speculation that the expression of
ECAD and NCAD in these neoplasms may have diagnostic significance.
OBJECTIVE: To investigate the utility of ECAD and NCAD immunoexpression
in distinguishing malignant (noncarcinomatous) neoplasms with
epithelioid features that involve the soft tissues. DESIGN: Membranous
immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived
cases selected from the files of the Armed Forces Institute of
Pathology. RESULTS: Epithelial-type cadherin was found in biphasic
synovial sarcoma (35 of 35 cases), malignant melanoma (13/21),
monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9),
poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma
(4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and
epithelioid sarcoma (5/62). Neural-type cadherin was observed in
chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse
mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma
(24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial
sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous
synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous
cell carcinomas all tested positive for ECAD, whereas NCAD was focally
observed in 5 cases. No expression of either molecule was observed in
cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part
sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7).
CONCLUSIONS: Epithelial-type and neural-type cadherins are found in a
variety of noncarcinomatous neoplasms with epithelioid features that
involve the soft tissues and can be utilized, in association with other
immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal
myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD),
squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD),
and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20%
ECAD).
12
UI - 11914621
AU - Aubry MC; Myers JL; Colby TV; Leslie KO; Tazelaar HD
TI -
Endometrial stromal sarcoma metastatic to the lung: a detailed analysis
of 16 patients.
SO - Am J Surg Pathol 2002 Apr;26(4):440-9
AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester,
Minnesota 55905, USA. aubry.mariechristine@mayo.edu
Pulmonary metastases of endometrial stromal sarcoma (ESS) are uncommon
and can pose diagnostic problems. We reviewed lung specimens from 16
patients with metastatic ESS. Patients were 31-77 years of age at the
time of lung biopsy. Uterine ESSs were diagnosed an average of 9.8 years
before lung biopsy in 11 patients. Uterine ESSs were originally called
smooth muscle tumors in three additional patients. Thirteen patients
were evaluated for new pulmonary nodules, seven of whom were
asymptomatic. Nodules were multiple in 14 and solitary in four, ranging
from 1.0 to 8.0 cm in greatest dimension. One patient died of metastatic
disease; 14 were alive and seven of these were without disease (mean
follow-up 4.1 years). Diagnostic considerations in 12 consultation cases
included ESS, sclerosing hemangioma, carcinoid tumor,
lymphangioleiomyomatosis, endometriosis, hemangiopericytoma, and
lymphoma. Tumors were well circumscribed and usually solid, composed of
plump spindle cells arranged in short fascicles. Two tumors were
predominantly cystic. Sex cord-like stromal differentiation was
identified in three. Neoplastic cells stained for vimentin (93%),
estrogen and progesterone receptor (100%), smooth muscle actin (57%),
desmin (50%), and keratin (46%). Metastatic ESS should be included in
the differential diagnosis of nonepithelial neoplasms in women.
13
UI - 11914631
AU - Dacic S; Finkelstein SD; Sasatomi E; Swalsky PA; Yousem SA
TI -
Molecular pathogenesis of pulmonary carcinosarcoma as determined by
microdissection-based allelotyping.
SO - Am J Surg Pathol 2002 Apr;26(4):510-6
AD - Department of Pathology, Division of Anatomic Pathology, University of
Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh,
Pennsylvania, USA. dacics@msx.upmc.edu
Pulmonary carcinosarcoma is a rare, biphasic tumor composed of malignant
epithelial and mesenchymal elements. Its histogenesis is controversial
in light of the presence of divergent cell lineages and the clonal
nature of malignancy. To address these issues, we performed an extensive
comparative genotypic analysis using microdissection to secure
representative mesenchymal and epithelial components from each of six
cases of pulmonary carcinosarcoma. Loss of heterozygosity was analyzed
with a panel of 12 polymorphic microsatellite markers designed to
indicate allelic loss and situated in proximity to known tumor
suppressor genes located on 1p, 3p, 5q, 9p, 10q, and 17p. In accordance
with the relatively greater biologic aggressiveness of this tumor type,
both the epithelial and mesenchymal components showed extensive allelic
loss, most notably for 3p, 5q, and 17p. More importantly, we found
overall equivalent patterns of acquired allelic loss between the two
components on an individual case basis, strongly supporting the
monoclonal origin of these neoplasms. Minor differences in the allelic
fingerprint between the two cell lineages could be explained by
progressive accumulation of allelic loss alterations that appear to
occur more frequently in the mesenchymal component of the tumor. The
data support the efficacy of microdissection-based allelic
fingerprinting to delineate the relationship between different
morphologic components of a single neoplasm.
14
UI - 11821409
AU - Bao KK; Skalka AM; Wong I
TI -
Presteady-state analysis of avian sarcoma virus integrase. I. A splicing
activity and structure-function implications for cognate site
recognition.
SO - J Biol Chem 2002 Apr 5;277(14):12089-98
AD - Department of Biochemistry and Biophysics, Oregon State University,
Corvallis, Oregon 97331, USA.
Integrase catalyzes insertion of a retroviral genome into the host
chromosome. After reverse transcription, integrase binds specifically to
the ends of the duplex retroviral DNA, endonucleolytically cleaves two
nucleotides from each 3'-end (the processing activity), and inserts
these ends into the host DNA (the joining activity) in a concerted
manner. In first-turnover experiments with synapsed DNA substrates, we
observed a novel splicing activity that resembles an integrase joining
reaction but uses unprocessed ends. This splicing reaction showed an
initial exponential phase (k(splicing) = 0.02 s(-1)) of product
formation and generated products macroscopically indistinguishable from
those created by the processing and joining activities, thus bringing
into question methods previously used to quantitate these reactions in a
time regime where multiple turnovers of the enzyme have occurred. With a
presteady-state assay, however, we were able to distinguish between
different pathways that led to formation of identical products.
Furthermore, the splicing reaction allowed characterization of substrate
binding and specificity. Although integrase requires only a 3' hydroxyl
with respect to nucleophiles derived from DNA, it specifically favors
the cognate sequence CATT as the electrophile. These experimental
results support a two-site "switching" model for binding and catalysis
of all three integrase activities.
15
UI - 11821408
AU - Bao KK; Skalka AM; Wong I
TI -
Presteady-state analysis of avian sarcoma virus integrase. II.
Reverse-polarity substrates identify preferential processing of the
U3-U5 pair.
SO - J Biol Chem 2002 Apr 5;277(14):12099-108
AD - Department of Biochemistry and Biophysics, Oregon State University,
Corvallis, Oregon 97331, USA.
The integrase-catalyzed insertion of the retroviral genome into the host
chromosome involves two reactions in vivo: 1) the binding and
endonucleolytic removal of the terminal dinucleotides of the viral DNA
termini and 2) the recombination of the ends with the host DNA. Kukolj
and Skalka (Kukolj, G., and Skalka, A. M. (1995) Genes Dev. 9,
2556-2567) have previously shown that tethering of the termini enhances
the endonucleolytic activities of integrase. We have used 5'-5'
phosphoramidites to design reverse-polarity tethers that allowed us to
examine the reactivity of two viral long terminal repeat-derived
sequences when concurrently bound to integrase and, additionally,
developed presteady-state assays to analyze the initial exponential
phase of the reaction, which is a measure of the amount of productive
nucleoprotein complexes formed during preincubation of integrase and
DNA. Furthermore, the reverse-polarity tether circumvents the
integrase-catalyzed splicing reaction (Bao, K., Skalka, A. M., and Wong,
I. (2002) J. Biol. Chem. 277, 12089-12098) that obscures accurate
analysis of the reactivities of synapsed DNA substrates. Consequently,
we were able to establish a lower limit of 0.2 s(-1) for the rate
constant of the processing reaction. The analysis showed the
physiologically relevant U3/U5 pair of viral ends to be the preferred
substrate for integrase with the U3/U3 combination favored over the
U5/U5 pair.
16
UI - 11955733
AU - Yap J; Chuba PJ; Thomas R; Aref A; Lucas D; Severson RK; Hamre M
TI -
Sarcoma as a second malignancy after treatment for breast cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1231-7
AD - Department of Radiation Oncology, Wayne State University School of
Medicine, Detroit, MI, USA.
BACKGROUND: Second malignant neoplasms may be a consequence of
radiotherapy for the treatment of breast cancer. Prior studies
evaluating sarcomas as second malignant neoplasms in breast cancer
patients have been limited by the numbers of patients and relatively low
incidence of sarcoma. Using data from the Surveillance, Epidemiology and
End Results registries, we evaluated the influence of radiation therapy
on the development of subsequent sarcomas in cases with primary breast
cancer. METHODS: Cases with primary invasive breast cancer (n = 274,572)
were identified in the Surveillance, Epidemiology and End Results Cancer
Incidence Public-Use Database (1973-1997). The database was then queried
to determine the cases developing subsequent sarcomas (n = 263).
Eighty-seven of these cases received radiation therapy, and 176 had no
radiation therapy. The cumulative incidence of developing secondary
sarcoma and the survival post developing secondary sarcoma were
determined by the Kaplan-Meier method. RESULTS: The occurrence of
sarcoma was low, regardless of whether cases received or did not receive
radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per
1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis,
respectively (p = 0.001). Of the sarcomas occurring within the field of
radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of
angiosarcomas occurring in cases not receiving radiotherapy. The
cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9
per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for
cases not receiving radiation (SE < 0.1). Overall survival was poor for
cases of sarcoma after breast cancer (27-35% at 5 years), but not
significantly different between patients receiving or not receiving
radiation therapy for their primary breast cancer. CONCLUSIONS:
Radiotherapy in the treatment of breast cancer is associated with an
increased risk of subsequent sarcoma, but the magnitude of this risk is
small. Angiosarcoma is significantly more prevalent in cases treated
with radiotherapy, occurring especially in or adjacent to the radiation
field. The small difference in risk of subsequent sarcoma for breast
cancer patients receiving radiotherapy does not supersede the benefit of
radiotherapy.
17
UI - 11955745
AU - Rovirosa A; Ascaso C; Ordi J; Abellana R; Arenas M; Lejarcegui JA;
TI -
Pahisa J; Puig-Tintore LM; Mellado B; Armenteros B; Iglesias X; Biete A
Is vascular and lymphatic space invasion a main prognostic factor in
uterine neoplasms with a sarcomatous component? A retrospective study of
prognostic factors of 60 patients stratified by stages.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1320-9
AD - Department of Radiation Oncology, Hospital Clinic i Universitari,
Barcelona, Spain. aroviro@medicina.ub.es
BACKGROUND: Sarcomatous neoplasms of the uterine corpus are still a
challenge in terms of obtaining prognostic factors and the most optimum
complementary treatment to surgery. The most important prognostic factor
is stage; relapses usually appear during the first 2 years, and most
patients die within the first 3 years. We have performed a multivariate
study of prognostic factors, stratifying patients by stage, to determine
their impact on overall survival, disease-free survival, local
relapse-free survival, and distant metastasis-free survival. Special
emphasis has been given to vascular and lymphatic space invasion (VLSI).
METHODS: Sixty patients diagnosed with uterine neoplasms with a main
sarcomatous component were treated at Hospital Clinic i Universitari of
carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial
stromal sarcomas. Treatment: 58/60 surgery, 35/60 postoperative
radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary
chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2
Stage IV. Variables analyzed: age, stage, vascular and lymphatic space
invasion, myometrial invasion, mitotic index, tumor size,
unicentricity/multicentricity, necrosis, and radiotherapy. Statistics:
the S and Cox proportional risk models. The partial effect of each risk
factor was calculated by hazard ratio (HR) with a confidence interval of
95%. RESULTS: Early stages: Multivariate analysis showed that tumor size
larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01
and HR = 24.45, respectively). VLSI was present in 23% of the cases.
Myometrial invasion greater than 50% had an impact on disease-free
survival and local relapse-free survival (HR was 9.75 and 3.20,
respectively). VLSI had an impact on distant metastasis-free survival
(HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only
leiomyosarcoma type made the overall survival worse (HR = 10.54).
CONCLUSIONS: Vascular and lymphatic space invasion was a relevant
prognostic factor in our series, with an impact on overall survival and
distant metastasis-free survival in early stages. In advanced stages,
VLSI had no impact on survival, but was present in 89% of cases.
Myometrial invasion >50% had an impact on local relapse. Advanced stages
had a more aggressive behavior, and there was a higher incidence of poor
prognostic factors in these stages. Nevertheless, prospective studies
are still needed on prognostic factors and on the best treatment option.
18
UI - 11955749
AU - Schwartz DL; Einck J; Hunt K; Bruckner J; Conrad E; Koh WJ; Laramore GE
TI -
The effect of delayed postoperative irradiation on local control of soft
tissue sarcomas of the extremity and torso.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1352-9
AD - Department of Radiation Oncology, Seattle VA Medical Center/Puget Sound
Health Care System, Seattle, WA 98108, USA. david.schwartz2@med.va.gov
PURPOSE: The impact of delayed adjuvant radiotherapy in patients treated
by surgical resection for peripheral or torso soft tissue sarcoma has
not been well characterized. We retrospectively examined this issue in
an institutional patient cohort. METHODS AND MATERIALS: One hundred two
adult patients were treated at the University of Washington Medical
Center between 1981 and 1998 with postoperative radiotherapy for cure of
a newly diagnosed soft tissue sarcoma. Of this group, 58 patients had
primary intermediate- or high-grade disease of the extremity or torso
(50 extremity/8 torso). Tumor histology was predominantly malignant
fibrohistiocytoma, synovial cell sarcoma, and leiomyosarcoma. The group
was dichotomized according to time interval from definitive resection to
the start of adjuvant radiation. Twenty-six patients had a short delay,
defined as <4 months, and 32 patients had a long delay of >or=4 months.
Both groups were balanced with regard to site, size, margin status, and
tumor depth; however, the long-delay group had a larger proportion of
high histologic grade lesions and was treated more frequently with
chemotherapy (31/32 [97%] for long-delay patients vs. 14/26 [54%] for
short-delay patients). Median follow-up was 49.5 months (range: 7-113
months). Median follow-up for patients still alive was 54 months (range:
9-113 months). Survival outcomes were estimated by the Kaplan-Meier
method. RESULTS: Overall local relapse-free survival at 5 years from the
time of definitive resection was 74%. On univariate analysis, estimated
5-year local relapse-free survival was significantly improved in the
short-delay group (88% vs. 62% for the long-delay group, p = 0.048 by
log rank). Overall distant relapse-free survival, disease-free survival,
and overall survival at 5 years were 77%, 68%, and 86%, respectively.
These survival outcomes were statistically equivalent in both radiation
delay groups. There was no evidence to suggest that delaying adjuvant
systemic therapy for postoperative radiation negatively impacted distant
relapse-free survival, disease-free survival, or overall survival.
Patterns of failure analysis revealed that 11/12 disease failures in the
long-delay group had a local component, with five patients presenting
with solitary local recurrences. Severe chronic radiation-related soft
tissue or peripheral nerve morbidity was infrequent (5/58 or 8.6%) and
similar in both groups. CONCLUSIONS: Postoperative radiation delays of 4
months or greater were associated with inferior local disease control
for intermediate- and high-grade soft tissue sarcomas of the extremity
and torso. Our results suggest that timing postoperative radiation
before postoperative chemotherapy may optimize local therapy for such
patients without adversely affecting distant disease control, long-term
morbidity, or overall survival. Prospective testing of this hypothesis
is warranted.
19
UI - 11957149
AU - Antonescu CR; Busam KJ; Iversen K; Kolb D; Coplan K; Spagnoli GC;
TI -
Ladanyi M; Old LJ; Jungbluth AA
MAGE antigen expression in monophasic and biphasic synovial sarcoma.
SO - Hum Pathol 2002 Feb;33(2):225-9
AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New
York, NY 10021, USA.
Synovial sarcomas are high-grade malignant mesenchymal tumors carrying a
pathognomonic cytogenetic alteration t(X;18) involving the SYT gene on
chromosome 18 and either SSX1 or SSX2 on chromosome X. Morphologically,
biphasic (BSS) and monophasic (MSS) variants can be distinguished.
Cancer/testis (CT) antigens are expressed in a variety of malignant
tumors, but not in normal tissues except in germ cells, primarily of the
testis. Anti-MAGE monoclonal antibody (mAb) 57B previously showed a high
incidence and homogenous reactivity pattern in a preliminary analysis of
synovial sarcomas. This study was performed to analyze the expression of
MAGE by immunohistochemistry with mAb 57B in 25 synovial sarcomas (12
monophasic, 13 biphasic), which were typed for the t(X;18)-derived
fusion transcript by reverse transcriptase polymerase chain reaction (19
SYT-SSX1, 6 SYT-SSX2). 57B immunoreactivity was present in 22 of 25
(88%) cases, and antigen expression was homogeneous in 14 of 22
57B-positive cases. Both morphological variants and both translocation
types were immunoreactive; three SYT-SSX1 tumors (one MSS, two BSS) were
57B negative. Our study demonstrates that MAGE is frequently and
homogeneously expressed in synovial sarcomas of both morphological
variants and both translocation types, making these tumors an attractive
target for MAGE antigen-based immunotherapy. Copyright 2002, Elsevier
Science (USA). All rights reserved.
20
UI - 11819129
AU - Imaizumi S; Morita T; Ogose A; Hotta T; Kobayashi H; Ito T; Hirata Y
TI -
Soft tissue sarcoma mimicking chronic hematoma: value of magnetic
resonance imaging in differential diagnosis.
SO - J Orthop Sci 2002;7(1):33-7
AD - Department of Orthopedic Surgery, Niigata Cancer Center Hospital, 2-15-3
Kawagishicho, Niigata 951-8133, Japan.
We report six patients with soft tissue sarcoma mimicking traumatic
hematoma. The lesions in these patients, showed huge hematomas and were
characterized by rapid growth. Cytology of percutaneous; aspiration
biopsy samples was performed in all six patients; however, in five
patients, findings for malignant cells were negative. Consequently, they
were misdiagnosed, resulting in a poor prognosis. We conducted a
retrospective study in which we evaluated the clinical findings, the
magnetic resonance (MR) images, and computed tomography (CT) scans of
the soft tissue sarcomas forming huge hematomas in the lesion. MR
imaging revealed the fine tumor mass with enhancement and characterized
the hematoma in the lesion in a more precise fashion than did CT. We
conclude that MR imaging is a suitable method for differentiating these
soft tissue sarcomas from chronic traumatic hematoma.
21
UI - 11845259
AU - Hernando JJ; Park TW; Kubler K; Offergeld R; Schlebusch H; Bauknecht T
TI -
Vaccination with autologous tumour antigen-pulsed dendritic cells in
advanced gynaecological malignancies: clinical and immunological
evaluation of a phase I trial.
SO - Cancer Immunol Immunother 2002 Mar;51(1):45-52
AD - Department of Obstetrics and Gynaecology, University of Bonn,
Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. j.hernando@uni-bonn.de
Dendritic cell (DC)-based therapy has proven to be effective in patients
with malignant lymphoma, melanoma, and renal and prostate carcinoma. In
this phase I clinical trial, we have shown that patients with advanced
gynaecological malignancies can be effectively vaccinated with DC pulsed
with keyhole limpet haemocyanin (KLH) and autologous tumour antigens.
Two patients with uterine sarcoma and six subjects with ovarian
carcinoma received three to 23 intracutaneous injections of
antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed
stable disease lasting 25 to 45 weeks, and five experienced tumour
progression within the first 14 weeks. KLH- and tumour lysate-specific
delayed-type hypersensitivity (DTH) reactions were observed in six and
one patient, respectively. Lymphoproliferative responses to KLH and to
tumour lysate stimulation were recorded in six patients and in two
patients respectively. Tumour antigen-stimulated interferon-gamma
(IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in
one patient was consistent with a T(H) type 1 cytokine bias. The
treatment was safe, well tolerated, immunologically active and except
for local cutaneous hypersensitivity devoid of significant adverse
effects.
22
UI - 7749711
AU - Zornig C; Peiper M; Schroder S
TI -
Re-excision of soft tissue sarcoma after inadequate initial operation.
SO - Br J Surg 1995 Feb;82(2):278-9
AD - Department of General Surgery, University Hospital Hamburg Eppendorf,
Germany.
sarcoma of the extremities and trunk underwent surgery and since 1988,
patients in whom the initial operation did not achieve safe margins
underwent reoperation (67 of the 189). At re-excision an en block
resection of the area with wide margins was achieved in 59 patients.
Residual tumour was found in 30 specimens (45 per cent). Thirty-six
patients received postoperative radiotherapy and/or chemotherapy. After
a mean follow-up of 32 (range 1-69) months five patients (7 per cent)
had local recurrence. In view of the high rate of local recurrence after
local excision of soft tissue sarcoma (70-90 per cent), primary
re-excision is indicated after an inadequate initial operation.
23
UI - 11578304
AU - Peiper M; Zornig C; Schroder S
TI -
Re-excision of soft tissue sarcoma after inadequate initial operation
(Br J Surg 1995; 82: 278-9).
SO - Br J Surg 2001 Oct;88(10):1417
24
UI - 11710636
AU - Helpap B
TI -
Nonepithelial neoplasms of the urinary bladder.
SO - Virchows Arch 2001 Oct;439(4):497-503
AD - Department of Pathology, Hegau-Klinikum Singen, University of Freiburg,
Germany. pathologie@hegau-klinikum.de
Nonepithelial tumors are rare in the urinary bladder, but their exact
classification is very important in the differential diagnosis between
these tumors and epithelial lesions. In the new WHO classification and
in the third series of the Armed Forces Institute of Pathology (AFIP)
"Atlas of Tumor Pathology" on urinary bladder tumors, various
mesenchymal tumors, mixed epithelial and mesenchymal tumors and
myofibroblastic proliferations are summarized. In the following we will
describe the histology, immunohistology, and cytogenetics of
nonepithelial tumors and lesions.
25
UI - 11903594
AU - Shimazaki K; Ohshima K; Haraoka S; Suzumiya J; Nakamura N; Kikuchi M
TI -
Accessory cell tumour: a clinicopathological study of 16 aggressive
tumours containing EBV-positive Hodgkin and Reed-Sternberg-like giant
cells.
SO - Histopathology 2002 Jan;40(1):12-21
AD - Department of Pathology, School of Medicine, Fukuoka University,
Nanakuma 7-45-1, Jonanku, Fukuoka 814-0180, Japan.
AIMS: Lymph nodes contain non-lymphoid accessory cells including
follicular dendritic cells and interdigitating dendritic cells.
Functionally, these cells belong to the category of immune accessory
cells involved in antigen presentation to B or T-lymphocytes. Neoplastic
proliferation of these cells is very uncommon. We present here the
clinicopathological features of 16 cases of accessory cell tumour.
METHODS AND RESULTS: We performed electron microscopic and
immunohistochemical examinations, and used in-situ hybridization for
EBV-encoded RNA (ISH-EBV) to detect the EBV genome in 11 cases, and
Southern blot analysis to assess EBV clonality in two cases. Tumour
cells were composed of oval-to-spindle cells arranged in diffuse, vague
storiform, fascicular and sometimes whorled patterns in a background of
small lymphocytes. In all cases, binucleated or multinucleated Hodgkin
and Reed-Sternberg-like giant cells were encountered. Staining for CD68
was positive in all cases. CD21, CD35, Ki-M4p, Ki-FDC1p, and S100
exhibited variable reactivity. ISH-EBV yielded positive labelling in
seven of 11 cases, of which five exhibited EBV only in Hodgkin and
Reed-Sternberg-like giant cells. Southern blot analysis showed clonality
of EBV terminal repeats (EBV-TR) in the two cases examined. Electron
microscopic examination showed that many of the tumour cells had
numerous interwoven long villous cell processes connected by occasional
desmosomes. Many tumours were very refractory to chemotherapy and
radiation, with a few exceptions, and half of the cases classified
initially as stage IV. A short survival time, of 10 months or less, was
observed in seven of 16 patients. CONCLUSIONS: Our study identified more
aggressive behaviour of accessory cell tumours. Our results suggest that
EBV may potentially induce activation of accessory cells to form Hodgkin
and Reed-Sternberg-like giant cells, which correspond with poor
prognosis.
26
UI - 11903598
AU - Kurian KM; Al-Nafussi A
TI -
Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological
study of 12 cases.
SO - Histopathology 2002 Jan;40(1):58-64
AD - Pathology Department, University of Edinburgh, 37 Liberton Brae,
Edinburgh EH16 6AG, UK. aan@srv4.med.ed.ac.uk
AIMS: To analyse the clinical and pathological features with long-term
follow-up of a series of 12 cases of sarcomatoid carcinoma of the
breast. methods and results: The cases were selected from the surgical
files of the Department of Pathology, University of Edinburgh, between
1977 and 1988. The following clinical parameters were recorded: the age
of the patients, size of tumour, presence or absence of lymph node or
distant metastases, and patient survival. Pathological assessment
included: the type of epithelial and mesenchymal components, the
proportion of monophasic to biphasic tumours and the presence of
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