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Abramson Cancer CenterNCI CANCERLIT® Search: Soft Tissue Sarcoma/Rhabdomyosarcoma - June 2002
National Cancer Institute®
Last Modified: June 1, 2002
- Evaluation of organ sparing operation results from planned indications in patients with kidney cancer.
- Gastrointestinal leiomyosarcomas.
- Menstrual and reproductive factors and risk of soft tissue sarcomas.
- Cytodifferentiation and clinical outcome after chemotherapy and radiation therapy for rhabdomyosarcoma (RMS).
- Topical topic: value of fine needle aspiration biopsy in childhood rhabdomyosarcoma: twenty-six years of experience in Slovenia.
- Review of a personal experience in the management of carcinomatosis and sarcomatosis.
- The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B
- Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production.
- Transcriptional downregulation of ORF50/Rta by methotrexate inhibits the switch of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
- Childhood cancer in Louisiana 1988-1996.
- Primary ophthalmic rhabdomyosarcoma in 33 patients.
- Rous sarcoma virus Gag protein-oligonucleotide interaction suggests a critical role for protein dimer formation in assembly.
- Kaposi's sarcoma-associated herpesvirus K3 utilizes the ubiquitin-proteasome system in routing class major histocompatibility
- Identification of amino acid residues of gp130 signal transducer and gp80 alpha receptor subunit that are involved in ligand binding and
- Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins.
- Management of soft-tissue sarcomas: an overview and update.
- Distinctive soft tissue tumors of the head and neck.
- Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of the uterus: a gynecologic oncology group study.
- Uterine sarcoma associated with tamoxifen use.
- Soft tissue sarcoma of the upper extremity: a 5-year experience at two institutions emphasizing the role of soft tissue flap reconstruction.
- Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas.
- Tumor volume as a prognostic factor for sarcomatosis.
- Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine
- [Update of orbital rhabdomyosarcoma therapy in children]
- [Ultrasonography of tumors of the locomotor system]
- A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7
- Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses.
- Radiation-induced secondary malignancy of the esophagus.
- Calponin and h-caldesmon expression in atypical fibroxanthoma and superficial leiomyosarcoma.
- PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group.
- Association of tamoxifen and uterine sarcoma.
- Soft tissue sarcoma in children: prognosis and management.
- Free microvascular flaps in oncological surgery of the limbs.
- Cancer/testis antigen CSAGE is concurrently expressed with MAGE in chondrosarcoma.
- Clinicopathological prognostic factors in soft tissue leiomyosarcoma: a multivariate analysis.
- Alveolar soft part sarcoma in children and adolescents: clinical features and outcome of 11 patients.
- Prognostic factors and treatment modalities in uterine sarcoma.
- Phyllodes tumors of the breast.
- Primary soft tissue sarcoma of the breast.
- [Mantel transplant for defect reconstruction after resection of malignant bone tumors of the lower extremity]
Table of Contents
1
UI - 11989552
AU - Fryczkowski M; Potyka A; Huk J
TI -
Evaluation of organ sparing operation results from planned indications
in patients with kidney cancer.
SO - Int Urol Nephrol 2001;32(4):621-7
AD - Department of Urology, Silesian Medical Academy, Zabrze, Poland.
An analysis in 53 patients with kidney cancer has been conducted, a
group on which kidney sparing operations have been performed. 25 women
and 28 men have been examined at the age of 53.7 in the postoperative
period of 7 divided by 130 months. The average observation time without
any recurrences or metastases was 48.8 months. 5.7% local and 1.9%
remote decease related recurrences have been found. The stage of
clinical progression and the degree of histological malignancy are
factors determining the five-year survival being 98.0%, while without
any recurrences or metastases being 88.4%.
2
UI - 11993598
AU - Casey RG; Garvey GP; Ryan J
TI -
Gastrointestinal leiomyosarcomas.
SO - Ir J Med Sci 2002 Jan-Mar;171(1):52
3
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.
4
UI - 11984800
AU - Smith LM; Anderson JR; Coffin CM
TI -
Cytodifferentiation and clinical outcome after chemotherapy and
radiation therapy for rhabdomyosarcoma (RMS).
SO - Med Pediatr Oncol 2002 Jun;38(6):398-404
AD - Department of Radiation Oncology, University of Utah Health Sciences
Center, Salt Lake City, Utah, USA. lynn.m.smith@hsc.utah.edu
BACKGROUND: Second-look surgery after therapy for rhabdomyosarcoma (RMS)
may yield prognostic information regarding tumor responsiveness to
treatment. Favorable outcome is suggested by tumor cells which have
undergone maturation (cytodifferentiation).PROCEDURE: Specimens from
patients treated on Intergroup RMS Study-IV (IRSG-IV) were studied
before and after treatment. All patients received chemotherapy and most
received radiation therapy. Post-treatment specimens were graded
according to the quantity of tumor showing cytodifferentiation (0 =
absent, 1 = mild, 2 = moderate, 3 = extensive). Proliferative activity
by MIB-1, topoisomerase II-alpha, and p53 protein expression were
measured. RESULTS: 19/31 cases from IRSG-IV were adequate for analysis.
Six out of nineteen patients failed therapy within 1.3 years of
treatment. Grade 3 cytodifferentiation was present in 10 cases (2 BRMS,
8 ERMS); none failed therapy. Grade 2 cytodifferentiation was present in
5 cases (1 ERMS, 2BRMS, 2ARMS); 2 patients with ARMS failed therapy.
Grade 0-1 cytodifferentiation was present in 4 cases (1 ERMS and 3
ARMS); all failed therapy. Proliferative activity by MIB-1 and
topoisomerase II-alpha immunohistochemistry decreased or was unchanged
after treatment for all ERMS/BRMS, and 4/5 cases of ARMS. p53
immunohistochemistry showed no consistent pattern of reactivity. Sparse
persistent tumor cells were present in 9/10 ERMS, 3/4 BRMS, 5/5 ARMS.
CONCLUSIONS: Extensive cytodifferentiation is more commonly seen in
ERMS/BRMS compared with less evidence for cytodifferentiation in ARMS
suggesting fundamentally different mechanisms of cellular response to
therapy in RMS. Sparse persistent tumor cells in post treatment
ERMS/BRMS specimens does not appear to affect outcome. Copyright 2002
Wiley-Liss, Inc.
5
UI - 11984803
AU - Pohar-Marinsek Z; Anzic J; Jereb B
TI -
Topical topic: value of fine needle aspiration biopsy in childhood
rhabdomyosarcoma: twenty-six years of experience in Slovenia.
SO - Med Pediatr Oncol 2002 Jun;38(6):416-20
AD - Department of Cytopathology, Institute of Oncology, Ljubljana, Slovenia.
BACKGROUND: Chemotherapy (Cht) for rhabdomyosarcoma (RMS) given before
local treatment can prevent mutilating surgery and high-dose irradiation
(RT). Fine needle aspiration biopsy (FNAB) can confirm the diagnosis and
neoadjuvant treatment can start without delay. The purpose of our study
was to assess the role of FNAB in the management of childhood RMS in
Slovenia. PROCEDURE: A total of 78 children and young adults were
included. FNAB provided the pre-treatment diagnosis in 37 and surgical
biopsy in 41 patients. In 61 cases recurrent/metastatic disease was
aspirated. Cytological diagnoses were compared to the original
histological diagnoses. All case histories, cytological and histological
material were reviewed and immunocytochemical staining performed when
necessary. RESULTS: FNAB provided a correct diagnosis of malignancy in
all 37 primary tumours, a specific diagnosis of RMS was given in 29
(78%). With the use of immunocytochemistry during the last 15 years, the
accuracy has risen to 87%. FNAB provided the diagnosis of
recurrence/metastasis in 57/61 cases. No complications of FNAB were
noted. Review of histology reclassified five original diagnoses of RMS
into one malignant rhabdoid tumour and four sarcomas NOS. In review of
cytology we were able to sub classify 80% of RMS. CONCLUSIONS: FNAB is a
safe method, which enables us to establish the pre-treatment diagnosis
of RMS, and to some extent even its type, without delay. In our study,
FNAB successfully replaced surgical biopsy in 87% of RMS patients during
the last 15 years. Neoadjuvant Cht was started immediately, surgery was
delayed and more conservative. Consequently, the risk for treatment
sequelae was considerably reduced. Copyright 2002 Wiley-Liss, Inc.
6
UI - 11902487
AU - Sugarbaker PH
TI -
Review of a personal experience in the management of carcinomatosis and
sarcomatosis.
SO - Jpn J Clin Oncol 2001 Dec;31(12):573-83
AD - Washington Cancer Institute, Washington Hospital Center, DC 20010, USA.
paul.surgarbuker@medstar.net
BACKGROUND: Peritoneal surface malignancy can result from seeding of
gastrointestinal cancer or abdomino-pelvic sarcoma; it can also occur as
a primary disease, such as peritoneal mesothelioma. In the past, this
clinical situation was treated only with palliative intent. METHODS: An
aggressive approach to peritoneal surface malignancy involves
peritonectomy procedures, perioperative intraperitoneal chemotherapy and
knowledgeable patient selection. The clinical assessments necessary for
valid clinical judgements include the cancer histopathology (invasive vs
expansive progression), the preoperative abdominal and pelvic CT, the
peritoneal cancer index and the completeness of cytoreduction score.
Proper patient selection is mandatory for optimizing the results of
treatment. RESULTS: In a series of phase II studies, appendiceal tumors
with peritoneal seeding became the paradigm for success with an 85%
long-term survival in selected patients. Carcinomatosis from colon
cancer had an overall 5-year survival of 50% with selected patients.
Also, sarcomatosis patients overall had a 40% 5-year survival in
selected patients. Peritoneal mesothelioma showed a 36% 5-year survival.
In all malignancies, early aggressive treatment of minimal peritoneal
surface dissemination showed the greatest benefit. CONCLUSIONS:
Oncologists must accept responsibility for knowledgeable management of
peritoneal surface dissemination of cancer because a curative approach
has been demonstrated in large phase II studies and all historical
controls show 0% long-term survival. Adjuvant phase III studies with
perioperative intraperitoneal chemotherapy in diseases where peritoneal
surface spread occurs are indicated.
7
UI - 11830587
AU - Liu L; Eby MT; Rathore N; Sinha SK; Kumar A; Chaudhary PM
TI -
The human herpes virus 8-encoded viral FLICE inhibitory protein
physically associates with and persistently activates the Ikappa B
kinase complex.
SO - J Biol Chem 2002 Apr 19;277(16):13745-51
AD - Hamon Center for Therapeutic Oncology Research and Division of
Hematology-Oncology, University of Texas Southwestern Medical Center,
Dallas, Texas 75390-8593, USA.
The human herpesvirus 8 (HHV8, also called Kaposi's sarcoma-associated
herpesvirus) has been linked to Kaposi's sarcoma and primary effusion
lymphoma (PEL) in immunocompromised individuals. We demonstrate that PEL
cell lines have a constitutively active NF-kappaB pathway, which is
associated with persistent phosphorylation of IkappaBalpha. To elucidate
the mechanism of NF-kappaB activation in PEL cell lines, we have
investigated the role of viral FLICE inhibitory protein (vFLIP) in this
process. We report that stable expression of HHV8 vFLIP in a variety of
cell lines is associated with persistent NF-kappaB activation caused by
constitutive phosphorylation of IkappaBalpha. HHV8 vFLIP gets recruited
to a approximately 700-kDa IkappaB kinase (IKK) complex and physically
associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP. HHV8 vFLIP is
incapable of activating NF-kappaB in cells deficient in NEMO/IKKgamma,
thereby suggesting an essential role of an intact IKK complex in this
process. Our results suggest that HHV8 vFLIP might contribute to the
persistent NF-kappaB activation observed in PEL cells by associating
with and stimulating the activity of the cellular IKK complex.
8
UI - 11967286
AU - Chung YH; Means RE; Choi JK; Lee BS; Jung JU
TI -
Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates
myeloid-lineage cells to induce inflammatory cytokine production.
SO - J Virol 2002 May;76(10):4688-98
AD - Department of Microbiology and Molecular Genetics and Tumor Virology
Division, New England Regional Primate Research Center, Harvard Medical
School, Southborough, Massachusetts 01772-9102, USA.
Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative
disease which is triggered by infection by Kaposi's sarcoma-associated
herpesvirus (KSHV). KSHV contains an open reading frame, K14, that has
significant homology with cellular OX2, designated viral OX2 (vOX2). In
this report, we demonstrate that vOX2 encodes a glycosylated cell
surface protein with an apparent molecular mass of 55 kDa. Purified
glycosylated vOX2 protein dramatically stimulated primary monocytes,
macrophages, and dendritic cells to produce the inflammatory cytokines
interleukin 1beta (IL-1beta), IL-6, monocyte chemoattractant protein 1,
and TNF-alpha. Furthermore, expression of vOX2 on B lymphocytes
stimulated monocytes to produce inflammatory cytokines in mixed culture.
These results demonstrate that like its cellular counterpart, vOX2
targets myeloid-lineage cells, but unlike cellular OX2, which delivers a
restrictive signal, KSHV vOX2 provides an activating signal, resulting
in the production of inflammatory cytokines. Thus, this is a novel viral
strategy where KSHV has acquired the cellular OX2 gene to induce
inflammatory cytokine production, which potentially promotes the
cytokine-mediated angiogenic proliferation of KSHV-infected cells.
9
UI - 11967335
AU - Curreli F; Cerimele F; Muralidhar S; Rosenthal LJ; Cesarman E;
TI -
Friedman-Kien AE; Flore O
Transcriptional downregulation of ORF50/Rta by methotrexate inhibits the
switch of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
from latency to lytic replication.
SO - J Virol 2002 May;76(10):5208-19
AD - Department of Microbiology, New York University School of Medicine, New
York, New York 10016, USA.
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cellular
dihydrofolate reductase (DHFR) homologue. Methotrexate (MTX), a potent
anti-inflammatory agent, inhibits cellular DHFR activity. We
investigated the effect of noncytotoxic doses of MTX on latency and
lytic KSHV replication in two KSHV-infected primary effusion lymphoma
cell lines (BC-3 and BC-1) and in MTX-resistant BC-3 cells (MTX-R-BC-3
cells). Treatment with MTX completely prevented tetradecanoyl phorbol
acetate-induced viral DNA replication and strongly decreased viral lytic
transcript levels, even in MTX-resistant cells. However, the same
treatment had no effect on transcription of cellular genes and KSHV
latent genes. One of the lytic transcripts inhibited by MTX, ORF50/Rta
(open reading frame), is an immediate-early gene encoding a
replication-transcription activator required for expression of other
viral lytic genes. Therefore, transcription of genes downstream of
ORF50/Rta was inhibited, including those encoding the viral
G-protein-coupled receptor (GPCR), viral interleukin-6, and K12/kaposin,
which have been shown to be transforming in vitro and oncogenic in mice.
Resistance to MTX has been documented in cultured cells and also in
patients treated with this drug. However, MTX showed an inhibitory
activity even in MTX-R-BC-3 cells. Two currently available
antiherpesvirus drugs, cidofovir and foscarnet, had no effect on the
transcription of these viral oncogenes and ORF50/Rta. MTX is the first
example of a compound shown to downregulate the expression of ORF50/Rta
and therefore prevent viral transforming gene transcription. Given that
the expression of these genes may be important for tumor development,
MTX could play a role in the future management of KSHV-associated
malignancies.
10
UI - 12014461
AU - Chen VW; Schmidt BA; Wu XC; Correa CN; Andrews PA; Hsieh MC; Ahmed MN
TI -
Childhood cancer in Louisiana 1988-1996.
SO - J La State Med Soc 2002 Mar-Apr;154(2):91-9
AD - Department of Public Health and Preventive Medicine/Louisiana Tumor
Registery at Louisiana Health Sciences Center, New Orleans, USA.
Utilizing data from the Louisiana Tumor Registry, cancer incidence among
children younger than 15 years of age is presented by major cancer type,
according to the primarily histology-based International Classification
of Childhood Cancer scheme. Cases include those diagnosed and/or treated
at any hospitals and medical facilities in Louisiana, St. Jude
Children's Research Hospital in Memphis, M.D. Anderson in Houston, and
from neighboring states. Rates were age-adjusted, presented as rates per
million, and were compared to the combined rates of the Surveillance,
Epidemiology, and End Results (SEER) Program. The significance of rate
differences were assessed at 0.05 level. From 1988-1996, about 125
children were diagnosed with cancer each year. In general, rates are
higher in younger than older children, males than females, and white
children than African-American children. The five most common childhood
cancers are: leukemias (28% of total cases), central nervous system
malignancies (22%), lymphomas (13%), renal tumors (8.4%), and soft
tissue sarcomas (7.6%). Major findings of these cancers and their
associated risk factors are presented.
11
UI - 11797301
AU - Shields CL; Shields JA; Honavar SG; Demirci H
TI -
Primary ophthalmic rhabdomyosarcoma in 33 patients.
SO - Trans Am Ophthalmol Soc 2001;99():133-42; discussion 142-3
AD - Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson
University, Philadelphia, Pennsylvania, USA.
PURPOSE: To review the findings, management, and outcome in 33 cases of
primary ophthalmic rhabdomyosarcoma. METHODS: The records of 33
consecutive patients from a single ocular oncology center were analyzed
retrospectively for outcomes of final visual acuity, local recurrence,
and distant metastasis. RESULTS: Rhabdomyosarcoma was primarily located
in the orbit m 25 cases (76%), conjunctiva in 4 (12%), eyelid in 1 (3%),
and uveal tract in 3 (9%). Findings had been present for a mean of 5
weeks and included proptosis in 10 patients (30%), eyelid swelling in 7
(21%), and blepharoptosis in 6 (18%). The initial diagnoses before
referral to us included primarily rhabdomyosarcoma in 8 cases (24%),
conjunctivitis in 5 (15%), cellulitis in 5 (15%), and pseudotumor in 4
(12%). Tumors were classified according to the Intergroup
Rhabdomyosarcoma Study Group staging and treatment protocols as group I
in 4 cases (12%), group II in 12 (36%), group III in 16 (48%), and group
IV in 1 case (3%). Treatment included surgical debulking, chemotherapy,
and radiotherapy. Local tumor recurrence was detected in 6 patients
(18%), lymph node spread in 2 (6%), and distant metastasis in 2 (6%).
Long-term visual outcome of the 28 patients who maintained their globe
was 20/20 to 20/40 in 11 patients (39%), 20/50 to 20/100 in 5 (18%), and
20/200 or worse in 12 (43%). Mean follow-up was 8.3 years; tumor-related
death occurred in 1 patients (3%). CONCLUSIONS: Rhabdomyosarcoma can
present in the orbit, eyelid, conjunctiva, and uveal tract. Following
treatment, local tumor recurrence occurs in 18% of cases, metastasis in
6%, and death in 3%.
12
UI - 11991973
AU - Ma YM; Vogt VM
TI -
Rous sarcoma virus Gag protein-oligonucleotide interaction suggests a
critical role for protein dimer formation in assembly.
SO - J Virol 2002 Jun;76(11):5452-62
AD - Department of Molecular Biology and Genetics, Cornell University,
Ithaca, New York 14853, USA.
The structural protein Gag is the only viral product required for
retrovirus assembly. Purified Gag proteins or fragments of Gag are able
in vitro to spontaneously form particles resembling immature virions,
but this process requires nucleic acid, as well as the nucleocapsid
domain of Gag. To examine the role of nucleic acid in the assembly in
vitro, we used a purified, slightly truncated version of the Rous
sarcoma virus Gag protein, Delta MBD Delta PR, and DNA oligonucleotides
composed of the simple repeating sequence GT. Apparent binding constants
were determined for oligonucleotides of different lengths, and from
these values the binding site size of the protein on the DNA was
calculated. The ability of the oligonucleotides to promote assembly in
vitro was assessed with a quantitative assay based on electron
microscopy. We found that excess zinc or magnesium ion inhibited the
formation of virus-like particles without interfering with protein-DNA
binding, implying that interaction with nucleic acid is necessary but
not sufficient for assembly in vitro. The binding site size of the Delta
MBD Delta PR protein, purified in the presence of EDTA to remove zinc
ions at the two cysteine-histidine motifs, was estimated to be 11
nucleotides (nt). This value decreased to 8 nt when the protein was
purified in the presence of low concentrations of zinc ions. The minimum
length of DNA oligonucleotide that promoted efficient assembly in vitro
was 22 nt for the zinc-free form of the protein and 16 nt for the
zinc-bound form. To account for this striking 1:2 ratio between binding
site size and oligonucleotide length requirement, we propose a model in
which the role of nucleic acid in assembly is to promote formation of a
species of Gag dimer, which itself is a critical intermediate in the
polymerizaton of Gag to form the protein shell of the immature virion.
13
UI - 11991980
AU - Lorenzo ME; Jung JU; Ploegh HL
TI -
Kaposi's sarcoma-associated herpesvirus K3 utilizes the
ubiquitin-proteasome system in routing class major histocompatibility
complexes to late endocytic compartments.
SO - J Virol 2002 Jun;76(11):5522-31
AD - Department of Pathology, Harvard Medical School, Boston Massachusetts
02115, USA.
Human herpesvirus 8 (HHV8) downregulates major histocompatibility
complex (MHC) class I complexes from the plasma membrane via two of its
genes, K3 and K5. The N termini of K3 and K5 contain a plant homeodomain
(PHD) predicted to be structurally similar to RING domains found in E3
ubiquitin ligases. In view of the importance of the ubiquitin-proteasome
system in sorting within the endocytic pathway, we analyzed its role in
downregulation of MHC class I complexes in cells expressing K3.
Proteasome inhibitors as well as cysteine and aspartyl protease
inhibitors stabilize MHC class I complexes in cells expressing K3.
However, proteasome inhibitors differentially affect sorting of MHC
class I complexes within the endocytic pathway and prevent their
delivery to a dense endosomal compartment. In this compartment, the
cytoplasmic tail of MHC class I complexes is cleaved by cysteine
proteases. The complex is then cleaved within the plane of the membrane
by an aspartyl protease, resulting in a soluble MHC class I fragment
composed of the lumenal domain of the heavy chain, beta(2)-microglobulin
(beta(2)m), and peptide. We conclude that K3 not only directs
internalization, but also targets MHC class I complexes to a dense
endocytic compartment on the way to lysosomes in a
ubiquitin-proteasome-dependent manner.
14
UI - 11991991
AU - Li H; Nicholas J
TI -
Identification of amino acid residues of gp130 signal transducer and
gp80 alpha receptor subunit that are involved in ligand binding and
signaling by human herpesvirus 8-encoded interleukin-6.
SO - J Virol 2002 Jun;76(11):5627-36
AD - Molecular Virology Laboratories, Department of Oncology, Johns Hopkins
University, Baltimore, Maryland 21231, USA.
Human herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the
gp130 signal transducer but is not dependent on the IL-6 receptor alpha
subunit (IL-6R, gp80) that is required for signaling by endogenous IL-6
proteins; however, IL-6R can enhance vIL-6 activity and can enable
signaling through a gp130 variant, gp130.PM5, that is itself unable to
support vIL-6 signaling. These findings suggest that the vIL-6-gp130
interactions are qualitatively different from those of human IL-6
(hIL-6) and that vIL-6 signaling may be more promiscuous than that of
hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To
examine the receptor binding requirements of vIL-6, we have undertaken
mutational analyses of regions of gp130 and IL-6R potentially involved
in interactions with ligand or in functional complex formation and used
these variants in functional, ligand-binding, and receptor dimerization
assays. The data presented identify positions within two interstrand
loops of the gp130 cytokine-receptor homology domain that are important
for vIL-6 signaling and vIL-6-induced receptor dimerization and show
that vIL-6, like hIL-6, can form complexes with IL-6R and gp130 but that
the roles of putative cytokine-binding residues of IL-6R in
ligand-induced functional complex formation are qualitatively different
in the case of vIL-6 and hIL-6.
15
UI - 11290599
AU - Wang QJ; Jenkins FJ; Jacobson LP; Kingsley LA; Day RD; Zhang ZW; Meng
TI -
YX; Pellett PE; Kousoulas KG; Baghian A; Rinaldo CR Jr; Pellet PE
Primary human herpesvirus 8 infection generates a broadly specific
CD8(+) T-cell response to viral lytic cycle proteins.
SO - Blood 2001 Apr 15;97(8):2366-73
AD - Department of Infectious Diseases and Microbiology, Graduate School of
Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus
that is the etiologic agent of Kaposi sarcoma (KS). The natural history
of primary HHV-8 infection, including clinical outcome and host immune
responses that may be important in preventing disease related to HHV-8,
has not been elucidated. The present study characterized the clinical,
immunologic, and virologic parameters of primary HHV-8 infection in 5
cases detected during a 15-year longitudinal study of 108 human
immunodeficiency virus type 1 seronegative men in the Multicenter AIDS
Cohort Study. Primary HHV-8 infection was associated with mild,
nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and
lymphadenopathy. There were no alterations in numbers of CD4(+) or
CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-gamma) production
to mitogen or nominal antigen. CD8(+) cytotoxic T-lymphocyte precursor
(CTLp) and IFN-gamma reactivity were detected during primary HHV-8
infection, with broad specificity to 5 lytic cycle proteins of HHV-8
encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of
Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein
homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early
protein homolog), in association with increases in serum antibody titers
and appearance of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell
responses to HHV-8 decreased by 2 to 3 years after primary infection.
This antiviral T-cell response may control initial HHV-8 infection and
prevent development of disease.
16
UI - 11905672
AU - Singer S; Demetri GD; Baldini EH; Fletcher CD
TI -
Management of soft-tissue sarcomas: an overview and update.
SO - Lancet Oncol 2000 Oct;1():75-85
AD - Division of Surgical Oncology, Brigham and Women's Hospital, Boston,
Massachusetts 02115, USA.
Soft-tissue sarcomas (STS) are relatively uncommon, especially when
considered as individual histological subtypes (of which there are more
than 50). Their incidence increases with age, although they are
disproportionately common among children. When diagnosed and managed in
a non-specialist environment, outcome is generally significantly poorer
than if patients are managed by a multidisciplinary team in a tertiary
centre of excellence. Prompt referral of patients with clinically
suspicious masses is strongly advocated, before any type of intervention
is attempted. This brief, opinion-based overview emphasises the team
approach and provides a synopsis of the strategies used at our
institution for pre-operative assessment and biopsy, surgical
management, and the delivery of radiation therapy when appropriate
(focusing on limb preservation and optimisation of function).
Predictable variations in the natural history of these tumours, based on
accurate histological subclassification, merit wider recognition. The
role of systemic chemotherapy for soft-tissue sarcoma is still evolving,
but at present the main aims are improved local control, disease-free
survival, and quality of life. There are overall survival benefits for
specific histological types, but this is a relatively small subgroup.
Novel therapies, based on disease mechanisms at the molecular level,
show promise for future advances.
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UI - 11904345
AU - Fletcher CD
TI -
Distinctive soft tissue tumors of the head and neck.
SO - Mod Pathol 2002 Mar;15(3):324-30
AD - Department of Pathology, Brigham & Women's Hospital and Harvard Medical
School, Boston, Massachusetts 02115, USA. cfletcher@partners.org
Among soft tissue tumors as a whole, those in the head and neck region
are relatively uncommon, and the proportion of all soft tissue sarcomas
that arise in this region is
UI - 11972393
AU - Fowler JM; Blessing JA; Burger RA; Malfetano JH
TI -
Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of
the uterus: a gynecologic oncology group study.
SO - Gynecol Oncol 2002 May;85(2):311-4
AD - Division of Gynecologic Oncology, Ohio State University, Columbus, OH
43210, USA.
OBJECTIVES: This is a Phase II group-wide study of the Gynecologic
Oncology Group to determine the toxicity and objective response rate of
trimetrexate (TMTX) in patients with advanced, persistent, or recurrent
mixed mesodermal tumors of the uterus who have failed higher priority
treatment protocols. METHODS: TMTX was administered orally at a dose of
5 mg/m(2) BID for 5 days and repeated in 14 days. The maximum total dose
was 50 mg/m(2)/week given every other week. The minimum treatment period
was one course. Patients who had a complete response, partial response,
or stable disease were continued on treatment for at least three
courses. RESULTS: Twenty-eight patients were entered into the study.
Three patients were ineligible based on review of pathologic materials.
Twenty-five patients were evaluable for toxicity, and 21 were evaluable
for response, as 4 patients did not complete one course of therapy.
Eleven patients had heterologous mixed mesodermal tumor (MMT) and 10 had
homologous MMT. Of the 25 evaluable for toxicity, one patient had grade
4 platelet toxicity. No patient had grade 4 neutropenia, while 4
patients had grade 3 decrease in absolute neutrophil count. One patient
had grade 3 gastrointestinal toxicity, while 2 had grade 4 toxicity.
There were no complete responses noted and only one partial response,
for an overall response rate of 4.8%. The duration of the partial
response was 15.2 months. CONCLUSION: Oral TMTX has insignificant
activity in the treatment of advanced, persistent, and recurrent uterine
MMT at the dose and schedule administered. (c) 2002 Elsevier Science
(USA).
UI - 12050351
AU - Wysowski DK; Honig SF; Beitz J
TI -
Uterine sarcoma associated with tamoxifen use.
SO - N Engl J Med 2002 Jun 6;346(23):1832-3
UI - 12001125
AU - Lohman RF; Nabawi AS; Reece GP; Pollock RE; Evans GR
TI -
Soft tissue sarcoma of the upper extremity: a 5-year experience at two
institutions emphasizing the role of soft tissue flap reconstruction.
SO - Cancer 2002 Apr 15;94(8):2256-64
AD - Section of Plastic Surgery, The University of Chicago, Chicago Illinois,
USA.
BACKGROUND: The objective of this study was to define the impact of soft
tissue flap reconstruction on multimodality therapy for patients with
soft tissue sarcomas of the upper extremity. Treatment standards
continue to evolve for these patients, and, with multimodality therapy,
most of them are candidates for limb-preserving surgery. Consequently,
the role of soft tissue flap reconstruction is expanding. METHODS: A
review was conducted of 100 consecutive patients with soft tissue
sarcomas of the upper extremity who underwent surgery at several
institutions between 1992 and 1997. RESULTS: Seventy-one patients
underwent direct closure of defects after tumor resection, and 29
patients required soft tissue reconstruction with flaps. These groups
were similar in most respects, except that 52% of the patients who
required soft tissue reconstruction presented with recurrent disease (P
= 0.0004), and 79% of them had tumors measuring > 5 cm in greatest
dimension (P = 0.0003). The patients who required flap reconstruction
had larger skin deficits after undergoing tumor resection (140 cm2)
compared with the patients who had wounds that were managed by direct
closure (40 cm2; P < 0.00001). Margins around the resected tumors were
larger (1.62 cm) when flaps were employed compared with margins when
defects were closed directly (0.87 cm; P = 0.0005). However, the number
of patients with intralesional, marginal, wide, and radical resections
was the same regardless of wound management. Major complications
occurred in 14% of patients, but none led to death or amputation. The
median follow-up was 31 months, and 66% of patients had no evidence of
disease at that time. Rates of local recurrence and survival were
similar for patients who underwent flap reconstruction compared with
patients who underwent direct closure. CONCLUSIONS: Soft tissue flap
reconstruction facilitates therapy for patients with soft tissue
sarcomas of the upper extremity, so that patients with larger tumors can
undergo resection, limiting complications and limb sacrifice. Copyright
2002 American Cancer Society.
UI - 12001127
AU - Aigner T; Muller S; Neureiter D; Illstrup DM; Kirchner T; Bjornsson J
TI -
Prognostic relevance of cell biologic and biochemical features in
conventional chondrosarcomas.
SO - Cancer 2002 Apr 15;94(8):2273-81
AD - Department of Pathology, University of Erlangen-Nurnberg, Erlangen,
Germany.
BACKGROUND: Conventional chondrosarcoma is the second most common
malignant solid tumor of bone, and its management still poses a
challenge for the orthopedic surgeon. Currently, tumor grade is the only
parameter of prognostic significance besides stage and, possibly,
resection margins. Additional independent prognostic markers therefore
would be highly valuable for patient management. METHODS: In the current
study, the authors evaluated biologic markers for various chondrocytic
phenotypes by histochemical and immunohistochemical technology in a
large series of clinically well defined cases of enchondromas and
conventional chondrosarcomas, each with at least 5 years of clinical
follow-up. RESULTS: The authors' results confirm the strong correlation
between clinical behavior and cell differentiation as expressed by
marker genes. The phenotypes of the tumor cells are the biologic
substrate of the histopathologic appearance of the neoplasms and, thus,
the biologic basis for classic tumor grading. Collagen Types II and X,
as well as the proteoglycan aggrecan, suggest a mature neoplastic
phenotype and good prognosis, i.e., low recurrence rate, rare
metastasis, and long survival. Conversely, collagen Type I, together
with cell spindling, indicates a transition to a more proliferative,
so-called "dedifferentiated" phenotype, which clearly is associated with
a poorer prognosis. The changes in cellular phenotypes are accompanied
by changes in proliferative activity. Thus, low-grade neoplasms showing
mainly mature and terminally differentiated (hypertrophic) chondrocytes
display only scant proliferation whereas less differentiated
chondrosarcomas with biologically dedifferentiated chondrocytes show
significantly higher proliferative activity, a feature that is also
highly correlated with prognosis. CONCLUSIONS: These data indicate that
molecular markers are to a large extent the biologic basis of the
conventional grading, rather than representing independent prognostic
markers. The authors' results further indicate that COL1 has significant
value in the distinction between enchondromas and low-grade
chondrosarcomas including these that are histologically similar. Further
understanding of chondrocytic phenotypes will be a promising way to
provide new tumor markers for better understanding, diagnosis, and
treatment of chondroid neoplasms. Copyright 2002 American Cancer
Society.
UI - 12015769
AU - Bilimoria MM; Holtz DJ; Mirza NQ; Feig BW; Pisters PW; Patel S; Pollock
TI -
RE; Benjamin RS; Papadopoulos NE; Plager C; Murphy A; Griffin JR;
Burgess MA; Hunt KK
Tumor volume as a prognostic factor for sarcomatosis.
SO - Cancer 2002 May 1;94(9):2441-6
AD - Department of Surgical Oncology, The University of Texas M.D. Anderson
Cancer Center, Houston, Texas 77030-4095, USA.
BACKGROUND: The appropriate therapeutic interventions for sarcomatosis,
or sarcoma characterized by intraabdominal dissemination, remain
unclear. The authors performed a retrospective analysis of their recent
experience with patients diagnosed with sarcomatosis to determine the
overall survival and the effects of clinicopathologic features on
survival rates at two and four years. METHODS: A query of the authors'
prospective soft tissue sarcoma database identified 51 patients with a
diagnosis of sarcomatosis who were evaluated at the authors' institution
evaluated, and survival was calculated using a Kaplan-Meier survival
analysis. Disease was categorized as low or high volume based on
findings at surgical exploration or computed tomography scan evaluation.
Disease was classified as low/intermediate grade or high grade based
upon histologic examination. RESULTS: Twenty five patients were male and
26 were female. The median time from the initial diagnosis of sarcoma to
the development of sarcomatosis was 0.9 years (range, 0-26 years).
Thirty nine patients were treated with surgery, whereas 32 received
primarily nonsurgical treatment. Histology revealed gastrointestinal
stromal tumor (GIST) in 33 patients and other histologies in 18
patients. The two year overall survival rate of patients with GIST was
similar to that of patients with other types of sarcoma (38% versus 42%,
respectively, P = 0.77). Patients with low volume disease had an overall
two year survival rate of 82%, compared with only 24% for patients with
high volume disease (P = 0.008). There was no difference in the overall
survival rates of patients with low grade (n = 18) versus high grade
tumors (n = 33, P = 0.29). With a median followup of 2.7 years (range,
0.5-26.4 years), the median time from sarcomatosis to death was 13
months (range, 4-42 months). CONCLUSIONS: Evaluating volume of disease
at the time of diagnosis permits stratification of patients into
prognosis based subsets. We found no significant difference in two or
four year survival rates in patients with GIST and those with non-GIST
sarcomatosis. Copyright 2002 American Cancer Society.DOI
10.1002/cncr.10504
UI - 12023578
AU - Folpe AL; Weiss SW
TI -
Lipoleiomyosarcoma (well-differentiated liposarcoma with
leiomyosarcomatous differentiation): a clinicopathologic study of nine
cases including one with dedifferentiation.
SO - Am J Surg Pathol 2002 Jun;26(6):742-9
AD - Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
afolpe@bellsouth.net
Leiomyosarcomatous (LMS) differentiation is a rare event in liposarcoma
(LPS) and may consist of either well-differentiated liposarcoma (WDL)
with an intrinsic smooth muscle component, so-called
"lipoleiomyosarcoma," (L-LMS) or dedifferentiated liposarcoma having
smooth muscle differentiation in the dedifferentiated zones. The latter
are high-grade sarcomas, whereas the behavior of the former group is
uncertain. Specifically, it is not clear whether the presence of LMS
negatively affects the prognosis. We present our experience with nine
cases, the largest to date. The patients (seven male, two female) ranged
in age from 42 to 65 years (mean 54 years). The tumors were usually
large (2 to >40 cm [mean 17 cm]) tumors in the retroperitoneum (two
cases), paratesticular-inguinal region (three cases), mediastinum (one
case), lung (one case), abdomen (one case), and popliteal fossa (one
case). The nine cases qualified as L-LMS and showed typical WDL with a
multifocal, gradual transition into smooth muscle areas. The latter
areas accounted for a variable portion of the lesions (range 5-90%) and
were of low cellularity, mild to moderate nuclear atypia, and low
mitotic activity. These areas seemed to arise from or blend with the
smooth muscle in the walls of large vessels within the tumor. One case
showed areas of dedifferentiation consisting of actin and
desmin-negative, high-grade sarcoma. Follow-up in seven cases (range
26-312 months; mean 119 months) showed multiple local recurrences in
seven patients and no metastases. Three patients are currently without
evidence of disease (follow-up duration 26-312 months; mean 144 months)
and four patients are alive with progressive disease (follow-up duration
60-132 months; mean 99 months). Our study suggests that L-LMS is a dual
lineage sarcoma as evidenced by the fact that the smooth muscle
component is often multifocal, not necessarily found in close
association with the atypical changes in fat, and seemingly originates
from atypical ("in situ") changes in the vessel wall. The LMS component,
which is typically low grade, does not adversely affect the overall
behavior of the tumor, which is similar to that of conventional WDL. LMS
in L-LMS should not be misconstrued as evidence of low-grade
dedifferentiation, a phenomenon that identifies a more unstable and
potentially metastasizing lesion.
UI - 11941256
AU - Ducrey N; Nenadov-Beck M; Spahn B
TI -
[Update of orbital rhabdomyosarcoma therapy in children]
SO - J Fr Ophtalmol 2002 Mar;25(3):298-302
AD - Service Universitaire d'ophtalmologie de Lausanne, Hopital Jules Gonin,
15 avenue de France, 1004 Lausanne.
INTRODUCTION: Rhabdomyosarcoma is the most frequent primitive orbital
malignant tumor in children. If the treatment is started as soon as
possible after discovery of the disease, the vital prognosis is
considerably better than otherwise. The goal of this paper is to present
the new therapeutic protocol and to report our experience in this field.
MATERIAL AND METHOD: During the past 35 years, 102 cases of orbital
tumors were collected in children under 15 years of age: 5 cases of
rhabdomyosarcoma were cared for in our department. At the time of tumor
diagnosis, the age of our patients ranged from 3 weeks to 13 years.
After a biopsy or excision biopsy, all our cases were treated by
chemotherapy with or without radiotherapy. Medication was mostly
vincristine, ifosfamide and actinomycine D. When the result of the
treatment was not satisfactory, carboplatine and epirubicine,
vincristine as well as ifosfamide were given. Radiotherapy was performed
only in particular cases or in recurrences. CONCLUSION: Rhabdomyosarcoma
is a highly malignant tumor. Although rare, it is the most frequent of
malignant tumors in children. It is important to keep it in mind in
order to perform a biopsy enabling quick diagnosis and treatment
following the modern protocol giving the highest chances of survival to
these patients: about 98% in 3 years.
UI - 11963481
AU - Mende U; Gutwein S; Krempien R; Wannenmacher M; Ewerbeck V; Worn H
TI -
[Ultrasonography of tumors of the locomotor system]
SO - Orthopade 2002 Feb;31(2):156-64
AD - Abteilung Klinische Radiologie und Poliklinik, Radiologische
Universitatsklinik, Im Neuenheimer Feld 400, 69120 Heidelberg.
ulrich_mende@med.uni-heidelberg.de
Sonography is an integral part of primary tumor diagnosis and follow-up
for the great majority of organ systems. However, its value in the field
of space-occupying processes of the locomotor system, especially of
malignant bone tumors, has mostly been underestimated. The sonographic
examination has to investigate the whole tumor region and the
corresponding lymph nodes statically and dynamically. The examination
procedure should be standardized and the documentation reliable.
Evaluation criteria are the localization, dimensions, and volume of the
tumors, echogenicity and homogeneity, peri- and intratumoral
vascularization (vessel density and architecture), borders of the tumor,
and neighboring structures. Pathologic changes not only of the soft
tissues but also of the bones can be evaluated sonographically. Even
subtle analysis does not permit definitive assessment of tumor status.
Taking its physical limitations into consideration, high-resolution
sonography, enhanced by color/PowerDoppler and three-dimensional
techniques, is a valuable adjunct to improve diagnosis, therapy
planning, monitoring, and posttherapeutic care of tumors of the
locomotor system.
UI - 11943871
AU - Zhu FX; King SM; Smith EJ; Levy DE; Yuan Y
TI -
A Kaposi's sarcoma-associated herpesviral protein inhibits
virus-mediated induction of type I interferon by blocking IRF-7
phosphorylation and nuclear accumulation.
SO - Proc Natl Acad Sci U S A 2002 Apr 16;99(8):5573-8
AD - Department of Microbiology, University of Pennsylvania School of Dental
Medicine, Philadelphia, PA 19104, USA.
Interferons constitute the earliest immune response against viral
infection. They elicit antiviral effects as well as multiple biological
responses involved in cell growth regulation and immune activation.
Because the interferon-induced cellular antiviral response is the
primary defense mechanism against viral infection, many viruses have
evolved strategies to antagonize the inhibitory effects of interferon.
Here, we demonstrate a strategy that Kaposi's sarcoma-associated
herpesvirus uses to block virus-mediated induction of type I interferon.
We found that a viral immediate-early protein, namely ORF45, interacts
with cellular interferon-regulatory factor 7 (IRF-7). In consequence,
IRF-7 phosphorylation is inhibited and the accumulation of IRF-7 in the
nucleus in response to viral infection is blocked. IRF-7 is a
transcription regulator that is responsible for virus-mediated
activation of type I interferon genes. By blocking the phosphorylation
and nuclear translocation of IRF-7, ORF45 efficiently inhibits the
activation of interferon alpha and beta genes during viral infection.
Inhibition of interferon gene expression through a viral protein
blocking the activation and nuclear translocation of a crucial
transcription factor is a novel mechanism for viral immune evasion.
UI - 11992546
AU - Panagopoulos I; Mertens F; Debiec-Rychter M; Isaksson M; Limon J; Kardas
TI -
I; Domanski HA; Sciot R; Perek D; Crnalic S; Larsson O; Mandahl N
Molecular genetic characterization of the EWS/ATF1 fusion gene in clear
cell sarcoma of tendons and aponeuroses.
SO - Int J Cancer 2002 Jun 1;99(4):560-7
AD - Department of Clinical Genetics, Lund University Hospital, SE-221 85
Lund, Sweden. Ioannis.Panagopoulos@klingen.lu.se
Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor
particularly associated with tendons and aponeuroses. The cytogenetic
hallmark is the translocation t(12;22)(q13;q12) resulting in a chimeric
EWS/ATF1 gene in which the 3'-terminal part of EWS at 22q is replaced by
the 3'-terminal part of ATF1 at 12q. To date, only 13 cases of CCS have
been analyzed for fusion genes at the transcription level, and there is
no information about the breakpoints at the genomic level. In the
present study, we describe the molecular genetic characteristics of CCS
from 10 patients. Karyotypes were obtained from 10 cases
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