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Abramson Cancer CenterNCI CANCERLIT® Search: Malignant Mesothelioma - September 2002
National Cancer Institute®
Last Modified: September 1, 2002
- Current therapy for malignant mesothelioma.
- Current surgical management of malignant pleural mesothelioma.
- Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin in patients with malignant pleural mesothelioma.
- Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic
- Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology.
- The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure.
- Statement on malignant mesothelioma in the United Kingdom.
- Diagnostic value of CYFRA 21-1 tumor marker and CEA in pleural effusion due to mesothelioma.
- Reappraisal of the strong association between simian virus 40 and human malignant mesothelioma of the pleura (Belgium).
- Phase II trial of pegylated-liposomal doxorubicin (Doxil) in mesothelioma.
- Stable disease in mesothelioma: a therapeutic achievement?
- Synergistic effect of the anti-HER-2/neu antibody and cisplatin in immortalized and primary mesothelioma cell lines.
- Presence of simian virus 40 (SV40) is not frequent in Swedish malignant mesotheliomas.
- Tremolite and mesothelioma.
- Overexpression of gamma-glutamylcysteine synthetase in human malignant mesothelioma.
- CT-guided percutaneous selective cordotomy for treatment of intractable pain in patients with malignant pleural mesothelioma.
- [Malignant mesothelioma in Emilia-Romagna: incidence and asbestos exposure]
- Assessment of malignant pleural mesothelioma with (18)F-FDG dual-head gamma-camera coincidence imaging: comparison with histopathology.
- A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma.
- Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies.
- Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and
Table of Contents
1
UI - 12044240
AU - Smythe WR
TI -
Current therapy for malignant mesothelioma.
SO - Curr Oncol Rep 2002 Jul;4(4):305-13
AD - Multidisciplinary Mesothelioma Thoracic Oncology Program, Department of
Thoracic and Cardiovascular Surgery, The University of Texas M.D.
Anderson Cancer Center, 1515 Holcombe Boulevard, Box 445, Houston, USA.
rsmythe@mail.mdanderson.org
This review briefly summarizes the results of previous systemic
(chemotherapy) and local (surgery and radiotherapy) treatment attempted
to date for malignant mesothelioma. The prospects for newer modalities,
ie molecular and biologic therapies, are also highlighted, including
results of both preclinical and early clinical research.
2
UI - 12044246
AU - Zellos L; Sugarbaker DJ
TI -
Current surgical management of malignant pleural mesothelioma.
SO - Curr Oncol Rep 2002 Jul;4(4):354-60
AD - Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard
Medical School, 75 Francis Street, Boston, MA 02115, USA.
Malignant pleural mesothelioma is a rare and very aggressive malignancy
with an increasing incidence. Single-modality therapy has failed to
improve median survival. Current surgical therapies include palliative
and cytoreductive procedures. The rarity of the disease, the lack of
randomized surgical studies, and the lack of a universally accepted and
validated staging system make it difficult to reach consensus and
establish stage-specific protocols. However, with strict criteria,
subsets of patients can be identified who can benefit from aggressive
cytoreductive surgical approaches, such as extrapleural pneumonectomy,
and adjuvant chemoradiation protocols. Our experience with this type of
protocol in carefully selected patients has resulted in increased median
survival. The lack of cure in any of the published protocols
demonstrates the need for new therapies and approaches for this disease.
3
UI - 12177114
AU - Hughes A; Calvert P; Azzabi A; Plummer R; Johnson R; Rusthoven J;
TI -
Griffin M; Fishwick K; Boddy AV; Verrill M; Calvert H
Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin
in patients with malignant pleural mesothelioma.
SO - J Clin Oncol 2002 Aug 15;20(16):3533-44
AD - Department of Medical Oncology, Northern Centre for Cancer Treatment,
Newcastle General Hospital, Westgate Road, Newcastle Upon Tyne NE4 6BE,
United Kingdom. andrew.hughes@newcastle.ac.uk
PURPOSE: To determine the maximum tolerated dose (MTD) of pemetrexed and
carboplatin given in combination, to derive a recommended dose for phase
II studies, and to explore its efficacy. We assessed toxicities and
explored the activity of the drug combination exclusively in patients
with malignant pleural mesothelioma (MPM). The pharmacokinetics of both
agents was investigated. PATIENTS AND METHODS: Twenty-seven patients (23
male, four female) with MPM were treated on five escalating dose levels.
Doses ranged from pemetrexed 400 mg/m(2) (as a 10-minute intravenous
infusion), followed by carboplatin area under the plasma
concentration-time curve (AUC) 4 mg/mL.min (as a 30-minute intravenous
infusion) to pemetrexed 500 mg/m(2), carboplatin AUC 6 mg/mL.min. All
patients had a World Health Organization performance status of 1. A
total of 163 courses of treatment were administered (median, six; range,
one to 10). RESULTS: The main toxicity was hematologic, particularly
neutropenia, although this was characteristically short-lived and caused
few clinical problems. The MTD was pemetrexed 500 mg/m(2), carboplatin
AUC 6, because three of the five patients treated at this dose level
experienced a dose-limiting toxicity. Eight partial responses (in 25
assessable patients) were observed for a response rate of 32%. Seventy
percent of patients noticed an improvement in symptoms, usually (84%)
after only two courses. Median time to progression was 305 days, and
median survival time was 451 days. CONCLUSION: The MTD was pemetrexed
500 mg/m(2) and carboplatin AUC 6 mg/mL.min. The recommended phase II
dose of the combination is pemetrexed 500 mg/m(2) and carboplatin AUC 5
mg/mL.min. The combination is both active and well tolerated in MPM and
deserves further exploration.
4
UI - 12115883
AU - Krismann M; Muller KM; Jaworska M; Johnen G
TI -
Molecular cytogenetic differences between histological subtypes of
malignant mesotheliomas: DNA cytometry and comparative genomic
hybridization of 90 cases.
SO - J Pathol 2002 Jul;197(3):363-71
AD - Institute of Pathology and German Mesothelioma Registry, University
Clinic, Bochum, Germany.
It is established that subtypes of human malignant mesotheliomas (MM)
are associated with different survival times. Ninety cases of MM were
examined using DNA cytometry and comparative genomic hybridization
(CGH), with emphasis on the main histological subtypes; epithelioid,
sarcomatoid and biphasic. A comparison by DNA cytometry revealed
moderate differences, with the rare subgroup of mesodermomas having the
highest and the sarcomatoid group the lowest rate of aneuploidy. Using
CGH, 6.2 chromosomal imbalances per case on average could be detected.
Losses (4.1/case) were more common than gains of chromosomal material
(2.1/case). MM show no single, specific defect, but a typical pattern of
genomic defects can be attributed to this tumour entity. Common losses
are clustered at the chromosomal regions 9p21 (34%), 22q (32%), 4q31-32
(29%), 4p12-13 (25%), 14q12-24 (23%), 1p21 (21%), 13q13-14 (19%), 3p21,
6q22, 10p13-pter and 17p12-pter (16% each). Common gains are located on
8q22-23 (18%), 1q23/1q32 (16%), 7p14-15 and 15q22-25 (14% each). While
differences in the frequencies of the defects between epithelioid and
sarcomatoid MM are not as pronounced as are seen with the pleomorphic
mesodermomas, several chromosomal locations (3p, 7q, 15q, 17p) show
significant variations. The most pronounced distinguishing feature of
sarcomatoid MM is a more than fourfold higher number of amplicons. These
data indicate that MM has a distinctive tumour biology with a broad
spectrum of heterogeneity, as reflected in morphology and also, more
subtly, in the patterns of chromosomal imbalances of the subtypes.
Copyright 2002 John Wiley & Sons, Ltd.
5
UI - 9375529
AU - McDonald AD; Case BW; Churg A; Dufresne A; Gibbs GW; Sebastien P;
TI -
McDonald JC
Mesothelioma in Quebec chrysotile miners and millers: epidemiology and
aetiology.
SO - Ann Occup Hyg 1997 Dec;41(6):707-19
AD - Department of Epidemiology, McGill University, Montreal, Canada.
In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec
chrysotile production industry, including a small asbestos products
factory, of 9780 men who survived into 1936, 8009 are known to have died
before 1993, 38 probably from mesothelioma--33 in miners and millers and
five in factory workers. Among the 5041 miners and millers at Thetford
Mines, there had been 4125 deaths from all causes, including 25 (0.61%)
from mesothelioma, a rate of 33.7 per 100,000 subject-years; the
corresponding figures for the 4031 men at Asbestos were eight out of
3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in
Asbestos, where all 708 employees were potentially exposed to
crocidolite and/or amosite, there were 553 deaths, of which five (0.90%)
were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was
3.5 times higher than among the local miners and millers. Six of the 33
cases in miners and millers were in men employed from 2 to 5 years and
who might have been exposed to asbestos elsewhere; otherwise, the 22
cases at Thetford were in men employed 20 years or more and the five at
Asbestos for at least 30 years. The cases at Thetford were more common
in miners than in millers, whereas those at. Asbestos were all in
millers. Within Thetford Mines, case-referent analyses showed a
substantially increased risk associated with years of employment in a
circumscribed group of five mines (Area A), but not in a peripherally
distributed group of ten mines (Area B); nor was the risk related to
years employed at Asbestos, either at the mine and mill or at the
factory. There was no indication that risks were affected by the level
of dust exposure. A similar pattern in the prevalence of pleural
calcification had been observed at Thetford Mines in the 1970s. These
geographical differences, both within the Thetford region and between it
and Asbestos, suggest that the explanation is mineralogical. Lung tissue
analyses showed that the concentration of tremolite fibres was much
higher in Area A than in Area B, a finding compatible with geological
knowledge of the region. These findings, probably related to the far
greater biopersistence of amphibole fibres than chrysotile, have
important implications in the control of asbestos related disease and
for wider aspects of fibre toxicology.
6
UI - 11108782
AU - Hodgson JT; Darnton A
TI -
The quantitative risks of mesothelioma and lung cancer in relation to
asbestos exposure.
SO - Ann Occup Hyg 2000 Dec;44(8):565-601
AD - Epidemiology and Medical Statistics Unit, Health and Safety Executive,
Magdalen House, Stanley Precinct, L20 3QZ, Bootle, UK.
john.hodgson@hse.gsi.gov.uk
Mortality reports on asbestos exposed cohorts which gave information on
exposure levels from which (as a minimum) a cohort average cumulative
exposure could be estimated were reviewed. At exposure levels seen in
occupational cohorts it is concluded that the exposure specific risk of
mesothelioma from the three principal commercial asbestos types is
broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite
respectively. For lung cancer the conclusions are less clear cut.
Cohorts exposed only to crocidolite or amosite record similar exposure
specific risk levels (around 5% excess lung cancer per f/ml.yr); but
chrysotile exposed cohorts show a less consistent picture, with a clear
discrepancy between the mortality experience of a cohort of xhrysotile
textile workers in Carolina and the Quebec miners cohort. Taking account
of the excess risk recorded by cohorts with mixed fibre exposures
(generally<1%), the Carolina experience looks uptypically high. It is
suggested that a best estimate lung cancer risk for chrysotile alone
would be 0.1%, with a highest reasonable estimate of 0.5%. The risk
differential between chrysotile and the two amphibole fibres for lunc
cancer is thus between 1:10 and 1:50.Examination of the inter-study dose
response relationship for the amphibole fibres suggests a non-linear
relationship for all three cancer endpoints (pleural and peritoneal
mesotheliomas, and lung cancer). The peritoneal mesothelioma risk is
proportional to the square of cumulative exposure, lung cancer risk lies
between a linear and square relationship and pleural mesothelioma seems
to rise less than linearly with cumulative dose. Although these
non-linear relationships provide a best fit ot the data, statistical and
other uncertainties mean that a linear relationship remains arguable for
pleural and lung tumours (but not or peritoneal tumours).Based on these
considerations, and a discussion fo the associated uncertainties, a
series of quantified risk summary statements for different elvels of
cumulative exposure are presented.
7
UI - 11254815
AU - British Thoracic Society Standards of Care Committee
TI -
Statement on malignant mesothelioma in the United Kingdom.
SO - Thorax 2001 Apr;56(4):250-65
8
UI - 11296181
AU - Paganuzzi M; Onetto M; Marroni P; Filiberti R; Tassara E; Parodi S;
TI -
Felletti R
Diagnostic value of CYFRA 21-1 tumor marker and CEA in pleural effusion
due to mesothelioma.
SO - Chest 2001 Apr;119(4):1138-42
AD - Clinical Pathology Laboratory, National Institute for Cancer Research,
Genoa, Italy. patclin@hp380.ist.unige.it
STUDY OBJECTIVE: The aim of our study was to assess the clinical value
of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as
diagnostic tools that are complementary to cytology in the diagnosis of
malignant mesotheliomas. PATIENTS: We measured CEA and CYFRA 21-1 in the
pleural effusions (PEs) and serum of 106 patients (benign lung disease,
34 patients; bronchogenic and metastatic carcinoma, 40 patients;
mesothelioma, 32 patients). METHODS: CEA and CYFRA 21--1 levels were
determined by means of two commercial enzyme immunoassays. RESULTS: The
cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the
basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL,
respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was
78% and 30.6%, respectively, with a specificity of 80% and 91%,
respectively. The sensitivity of CYFRA 21--1 and CEA in patients with
mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA
21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with
a negative or uncertain cytology. The association of the tumor marker
assay and the cytology allowed a correct diagnosis in 30 of 32 cases of
mesothelioma (93.7%). CONCLUSION: This study suggests that CYFRA 21--1
would provide a useful parameter for the differential diagnosis between
benign and malignant PE from mesothelioma when the result of cytology is
negative or uncertain and the clinical context does not allow a more
aggressive approach. Moreover, the association of CYFRA 21--1 with CEA
could provide details for a differential diagnosis between mesotheliomas
and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA
level is highly suggestive of mesothelioma, whereas high levels of CEA
alone or high levels of both the markers suggest a diagnosis of
malignant PE, excluding mesothelioma.
9
UI - 11936818
AU - Hubner R; Van ME
TI -
Reappraisal of the strong association between simian virus 40 and human
malignant mesothelioma of the pleura (Belgium).
SO - Cancer Causes Control 2002 Mar;13(2):121-9
AD - Laboratory of Pathology, University of Antwerp, Wilrijk, Belgium.
roland.hubner@ua.ac.be
OBJECTIVE: The frequent association of a monkey oncogenic virus, simian
virus 40 (SV40), with pleural mesothelioma and the proposed transmission
of the virus from contaminated polio vaccines to humans has received
considerable scientific and public attention. We sought to determine
whether SV40 would indeed be present in mesothelioma patients from
Belgium, as claimed in former studies, and to characterize the viral
genome in respective specimens. METHODS: DNA was extracted from frozen
tissue from 12 patients diagnosed with pleural mesothelioma in Belgium.
Five different extraction methods were compared and primer pairs
targeting four informative regions of the SV40 genome were used to
amplify viral products by the polymerase chain reaction (PCR). One of
the pairs additionally allows amplification of human polyoma viruses.
Southern blotting with an oligonucleotide probe directed at the expected
SV40 sequences was also applied. RESULTS: One of the 12 samples
contained amplifiable JC virus DNA. In contrast, none of the samples
(0/12, 95% CI 0% to 26.5%) was positive for SV40 DNA sequences. The
Southern blot analysis confirmed the absence of trace amounts of SV40
PCR product. We also clearly demonstrate that an otherwise specific
probe against SV40 could easily hybridize in quite a non-specific manner
under recommended conditions. CONCLUSIONS: These results provide strong
evidence for a lack of association of SV40 with most pleural
mesotheliomas in the Belgian population. We recommend a re-examination
of other positive case series and avoidance of questionable
hybridization practices in future studies.
10
UI - 12197225
AU - Skubitz KM
TI -
Phase II trial of pegylated-liposomal doxorubicin (Doxil) in
mesothelioma.
SO - Cancer Invest 2002;20(5-6):693-9
AD - University of Minnesota Medical School, Masonic Cancer Center,
Minneapolis, MN 55455, USA.
Pegylated-liposomal doxorubicin (Doxil) is a form of liposomal
doxorubicin in which the liposomes are coated with methoxypoly(ethylene
glycol), resulting in a diminished uptake by the reticuloendothelial
system, a longer half-life in blood, and a different toxicity profile
than nonpegylated liposomes. A phase II study of Doxil in mesothelioma
was performed. The initial dose per course was 55 mg/m2 every 4 weeks
with dose modification based on mucositis and hand-foot syndrome (the
main limiting toxicities). Treatment was generally well tolerated. Of 73
evaluable treatment courses in 15 patients, toxicities were mild and
similar to previous reports, but dose reduction was common. No definite
cardiac toxicity was observed. Fourteen patients were evaluable for
response; four of the 15 patients treated responded meaningfully. These
data suggest that pegylated-liposomal doxorubicin has activity in
mesothelioma, and that this treatment is associated with modest
toxicity.
11
UI - 12197248
AU - Muggia F
TI -
Stable disease in mesothelioma: a therapeutic achievement?
SO - Cancer Invest 2002;20(5-6):859-60
12
UI - 12209878
AU - Toma S; Colucci L; Scarabelli L; Scaramuccia A; Emionite L; Betta PG;
TI -
Mutti L
Synergistic effect of the anti-HER-2/neu antibody and cisplatin in
immortalized and primary mesothelioma cell lines.
SO - J Cell Physiol 2002 Oct;193(1):37-41
AD - Department of Oncology, Biology and Genetics, University of Genoa,
Italy. toma@cba.unige.it
Malignant mesothelioma (MM) still remains a therapeutic and diagnostic
problem to which new therapeutic perspectives are being continuously
tried and tested. Three different primary cultures (MMGe-1, MES MM 98,
and MES 1) and one immortalized cell line (MSTO 211 H) of human MM were
studied in order to evaluate the HER-2/neu expression. Three out of four
cell lines showed a different level of c-erbB-2 expression, the highest
being detected on the MSTO 211 H cell line (fibroblastic phenotype),
whereas MMGe-1 resulted negative. The effect of the anti-HER-2/neu
antibody (Trastuzumab) alone, and in combination with cisplatin (CDDP)
at different doses (ranging from 0.1 to 100 microg/ml), was studied on
all the c-erB-2 positive cell lines. Trastuzumab was able to inhibit
cell proliferation in a time-dependent manner, with growth inhibition
also obtained at low concentrations (0.1-1 microg/ml). Combined
treatment with Trastuzumab (10 microg/ml) and CDDP (1 microg/ml) showed
synergism. Our results were encouraging, and suggest a rationale for
further investigations in a clinical setting. Copyright 2002 Wiley-Liss,
Inc.
13
UI - 12168811
AU - Priftakis P; Bogdanovic G; Hjerpe A; Dalianis T
TI -
Presence of simian virus 40 (SV40) is not frequent in Swedish malignant
mesotheliomas.
SO - Anticancer Res 2002 May-Jun;22(3):1357-60
AD - Department of Oncology-Pathology, Karolinska Institute, Karolinska
Hospital, Stockholm, Sweden. peter.priftakis@cck.ki.se
Simian virus 40 (SV40), a contaminant of polio vaccines used in the
United States and Europe between 1955 and 1963, has been detected with
high frequency in human malignant mesotheliomas (MM). In Sweden, from
1958, due to production in Javanese macaque kidney cells and SV40
testing from 1961, only polio vaccine claimed to be free of SV40 has
been used. Hence, we aimed to screen Swedish MM patients for the
presence of SV40. MATERIALS AND METHODS: Forty-one paraffin-embedded
pleural MM samples, obtained from patients born from 1893-1958, were
examined for amplifiable DNA. Testable samples were thereafter evaluated
for the presence of SV40 DNA by two types of polymerase chain reactions
(PCR) followed by sequencing. RESULTS: SV40 could be confirmed by
sequencing in only 3 of the 30 MM samples containing DNA that could be
amplified by PCR. CONCLUSION: The presence of SV40 is not frequent in
Swedish MM patients.
14
UI - 12176759
AU - Roggli VL; Vollmer RT; Butnor KJ; Sporn TA
TI -
Tremolite and mesothelioma.
SO - Ann Occup Hyg 2002 Jul;46(5):447-53
AD - Department of Pathology, Duke University and Durham VA Medical Centers,
NC 27710, USA. roggli.v@durham.va.gov
BACKGROUND: Exposure to chrysotile dust has been associated with the
development of mesothelioma and recent studies have implicated
contaminating tremolite fibers as the likely etiological factor.
Tremolite also contaminates talc, the most common non-asbestos mineral
fiber in our control cases. METHODS: We examined 312 cases of
mesothelioma for which fiber burden analyses of lung parenchyma had been
performed by means of scanning electron microscopy to determine the
content of tremolite, non-commercial amphiboles, talc and chrysotile.
The vast majority of these patients were exposed to dust from products
containing asbestos. RESULTS: Tremolite was identified in 166 of 312
cases (53%) and was increased above background levels in 81 cases (26%).
Fibrous talc was identified in 193 cases (62%) and correlated strongly
with the tremolite content (P < 0.0001). Chrysotile was identified in
only 32 cases (10%), but still correlated strongly with the tremolite
content (P < 0.0001). Talc levels explained less of the tremolite
deviance for cases with an increased tremolite level than for cases with
a normal range tremolite level (22 versus 42%). In 14 cases (4.5%)
non-commercial amphibole fibers (tremolite, actinolite and/or
anthophyllite) were the only fiber types found above background.
CONCLUSIONS: We conclude that tremolite in lung tissue samples from
mesothelioma victims derives from both talc and chrysotile and that
tremolite accounts for a considerable fraction of the excess fiber
burden in end-users of asbestos products.
15
UI - 12196927
AU - Jarvinen K; Soini Y; Kahlos K; Kinnula VL
TI -
Overexpression of gamma-glutamylcysteine synthetase in human malignant
mesothelioma.
SO - Hum Pathol 2002 Jul;33(7):748-55
AD - Department of Internal Medicine, University of Oulu, Helsinki, Finland.
Mesothelioma is a fatal tumor resistant to all treatment modalities for
reasons that are still unresolved. Glutathione (GSH)-associated pathways
are induced by oxidants and cytotoxic drugs, and they are also involved
in the progression and resistance of some tumor cells in vitro. The
rate-limiting enzyme in GSH biosynthesis is gamma-glutamylcysteine
synthetase (gamma GCS). However, the expression of this enzyme has not
been systematically investigated in malignant tumors, and there are no
studies of gamma GCS in biopsy specimens of malignant mesothelioma. We
investigated the immunohistochemical distribution and expression of both
subunits of gamma GCS in healthy pleural mesothelium, pleural
mesothelioma tumor biopsy samples (34 cases), and mesothelioma cells in
culture (7 cell lines). Nonmalignant mesothelium showed no
immunoreactivity for either subunit in any of the cases. The heavy
(catalytic) subunit of gamma GCS was highly immunostained in 29 and
weakly positive in 5 cases. High-moderate and weak immunoreactivity of
the light (regulatory) subunit of gamma GCS was found in 15 and 7
tumors, respectively, whereas 12 cases showed no reactivity. There was
no correlation with either catalytic or regulatory subunit expression
and patient survival. There was, however, a significant correlation
between the heavy chain and multidrug resistance protein (MRP) 2 (P
=.048), whereas no correlation was observed between the light chain and
MRP1 or MRP2. Treatment of cultured mesothelioma cells with buthionine
sulfoximine (BSO), to inhibit gamma GCS, significantly potentiated
cisplatin-induced cytotoxicity mainly by nonapoptotic mechanism when
assessed by counting the living cells, TUNEL (terminal
deoxytransferase-mediated dUTP nick-end labeling) assay, and caspase-3
cleavage. In conclusion, gamma GCS is highly positive in most cases of
malignant mesothelioma and may play an important role in the primary
drug resistance of this tumor in vivo. Copyright 2002, Elsevier Science
(USA). All rights reserved.
16
UI - 12111493
AU - Kanpolat Y; Savas A; Ucar T; Torun F
TI -
CT-guided percutaneous selective cordotomy for treatment of intractable
pain in patients with malignant pleural mesothelioma.
SO - Acta Neurochir (Wien) 2002 Jun;144(6):595-9; discussion 599
AD - Department of Neurosurgery, Ankara University, School of Medicine,
Ankara, Turkey.
Malignant mesotheliomas are neoplasms that arise from mesothelial cells
and cause intractable pain in the chest wall, usually located
unilaterally. This local pain can be well controlled by computerized
tomography (CT)-guided percutaneous cordotomy (PC). One hundred and
fifty-three patients suffering from intractable pain due to malignancy
were treated with CT-guided cordotomy between 1988 and 2001. Seventy of
the 153 patients had pulmonary malignancy. Among these, 40 had
bronchogenic carcinoma, 11 had Pancoast tumors and the remaining 19 had
mesothelioma. The latter 19 cases with malignant mesothelioma suffering
from unilateral pain were treated with CT-guided PC. In 18 cases, pain
was controlled totally and, in one, partial pain control was obtained.
Selective pain control was obtained in 15 cases, in whom narcotic drugs
were discontinued postoperatively. Post-cordotomy dysesthesia was noted
in only one case, and no complication or mortality was observed. In the
treatment of intractable pain, CT-guided cordotomy is a perfect method
in selected cases with malignancy. This is the most effective and
suitable treatment modality for local pain due to malignant
mesothelioma.
17
UI - 12197049
AU - Mangone L; Romanelli A; Campari C; Candela S
TI -
[Malignant mesothelioma in Emilia-Romagna: incidence and asbestos
exposure]
SO - Epidemiol Prev 2002 May-Jun;26(3):124-9
AD - Registro Mesoteliomi della Regione Emilia-Romagna, Dipartimento di
sanita pubblica, AUSL Reggio Emilia.
This paper describes the activity, the sources of informations, methods
and results of the "Emilia-Romagna Mesothelioma Registry" (ReM). The
Registry started in 1996 and collects all cases of Malignant
Mesothelioma (MM) occurring in Emilia-Romagna. 323 new cases (225 males
and 98 females) have been detected during the period 1996-2001. Most
cases (n = 286) concerned pleura. Other observed localizations were:
peritoneum (n = 30), tunica vaginalis testis (n = 4) and pericardium (n
= 3). Most of the cases were reported by the Institutes of Pathology and
Occupational Health and by the Safety Services (respectively the 62% and
the 18%). 87% of all the cases were histologically, 8% TC, 4%
radiologically and only 1% clinically confirmed. The regional incidence
rate (for 10(5) person-years, age standardized on the 1991 Italian
population), has been estimated to be 1.98 in males and 0.88 in females.
The highest rates were registered in Piacenza and Reggio Emilia province
among men and Reggio Emilia and Ravenna province among women. 72% of
cases have been classified as exposed to asbestos (64% occupationally
and 8% as domestic/environmentally exposed).
18
UI - 12215551
AU - Gerbaudo VH; Sugarbaker DJ; Britz-Cunningham S; Di Carli MF; Mauceri C;
TI -
Treves ST
Assessment of malignant pleural mesothelioma with (18)F-FDG dual-head
gamma-camera coincidence imaging: comparison with histopathology.
SO - J Nucl Med 2002 Sep;43(9):1144-9
AD - Division of Nuclear Medicine, Department of Radiology, Brigham and
Women's Hospital and Harvard Medical School, Boston, Massachusetts
02115, USA. vgerbaudo@bics.bwh.harvard.edu
Malignant pleural mesothelioma is an aggressive primary neoplasm for
which early detection and accurate staging are known diagnostic
challenges. The role of (18)F-FDG dual-head gamma-camera coincidence
imaging ((18)F-FDG-CI) is yet to be defined. The purpose of this study
was to evaluate the usefulness of (18)F-FDG-CI in the assessment of
malignant pleural mesothelioma using histopathology as the gold
standard. METHODS: Fifteen consecutive patients with CT scan evidence of
pleural thickening, fluid, plaques, or calcification underwent (18)F-FDG
imaging 1.5 h after the intravenous administration of 370 MBq (18)F-FDG.
Imaging was performed with a dual-head gamma camera equipped with
2.54-cm-thick NaI crystals operating in coincidence mode. Using an
iterative algorithm, whole-body images were reconstructed as transaxial,
sagittal, and coronal images. No attenuation correction was applied. The
results of (18)F-FDG-CI scans were compared with CT and with
histopathologic diagnosis. RESULTS: Eleven of 15 patients had
histologically proven malignant mesotheliomas (10 epithelial, 1
sarcomatoid). All 11 primary tumors were detected by (18)F-FDG, and
absence of disease was confirmed in the 4 patients who were disease
free. Thirty-four lesions were biopsied; among these, 29 were found to
be positive for tumor. (18)F-FDG was true-positive in 28 lesions,
true-negative in 4, false-negative in 1 (0.5 cm in diameter), and
false-positive in 1 (inflammatory pleuritis). The smallest lesion
detected was 0.8 cm. For biopsied lesions, overall sensitivity,
specificity, and accuracy for (18)F-FDG-CI were 97%, 80%, and 94%
respectively, compared with 83%, 80%, and 82% for CT. Twenty-one of 29
positive lesions involved the pleura, lung parenchyma, or chest wall and
were all (18)F-FDG avid. In the mediastinum, (18)F-FDG-CI detected 7 of
8 biopsy-positive lesions (88%), whereas CT was positive in 6 of 8
lesions (75%). (18)F-FDG identified extrathoracic metastases in 5
patients, excluding them from surgical therapy. CONCLUSION: These
preliminary results suggest that (18)F-FDG-CI appears to be an accurate
method to diagnose and to define the extent of disease in patients with
diffuse malignant pleural mesothelioma.
19
UI - 12189542
AU - Nowak AK; Byrne MJ; Williamson R; Ryan G; Segal A; Fielding D; Mitchell
TI -
P; Musk AW; Robinson BW
A multicentre phase II study of cisplatin and gemcitabine for malignant
mesothelioma.
SO - Br J Cancer 2002 Aug 27;87(5):491-6
AD - Department of Medical Oncology, Sir Charles Gairdner Hospital, Verdun
Street, Nedlands, WA 6009 Australia.
Our previous phase II study of cisplatin and gemcitabine in malignant
mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with
symptom improvement in responding patients. Here we confirm these
findings in a multicentre setting, and assess the effect of this
treatment on quality of life and pulmonary function. Fifty-three
patients with pleural malignant mesothelioma received cisplatin 100 mg
m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of
a 28 day cycle for a maximum of six cycles. Quality of life and
pulmonary function were assessed at each cycle. The best response
achieved in 52 assessable patients was: partial response, 17 (33%, 95%
CI 20-46%); stable disease, 31 (60%); and progressive disease, four
(8%). The median time to disease progression was 6.4 months, median
survival from start of treatment 11.2 months, and median survival from
diagnosis 17.3 months. Vital capacity and global quality of life
remained stable in all patients and improved significantly in responding
patients. Major toxicities were haematological, limiting the mean
relative dose intensity of gemcitabine to 75%. This schedule of
cisplatin and gemcitabine is active in malignant mesothelioma in a
multicentre setting. Investigation of alternative scheduling is needed
to decrease haematological toxicity and increase the relative dose
intensity of gemcitabine whilst maintaining response rate and quality of
life.
20
UI - 12194995
AU - Abutaily AS; Addis BJ; Roche WR
TI -
Immunohistochemistry in the distinction between malignant mesothelioma
and pulmonary adenocarcinoma: a critical evaluation of new antibodies.
SO - J Clin Pathol 2002 Sep;55(9):662-8
AD - Respiratory Cell and Molecular Biology, University of Southampton,
University of Southampton, Southampton General Hospital, UK.
AIM: The value of immunohistochemical staining in differentiating
between malignant mesothelioma and pulmonary adenocarcinoma was
re-examined using newly available commercial antibodies, with the aim of
increasing the sensitivity and specificity of diagnosis, and simplifying
the antibody panel required. METHODS: Forty one malignant mesotheliomas
and 35 lung adenocarcinomas were studied. Commercial antibodies to
calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A),
thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin
5/6 were applied using the streptavidin-biotin-peroxidase complex
procedure on formalin fixed, paraffin wax embedded tissue. RESULTS:
E-cadherin was expressed in all adenocarcinomas and in 22% of the
mesotheliomas. TTF-1 expression was detected in 69% of the
adenocarcinomas and none of the mesotheliomas. Positive staining with
polyclonal anticalretinin was detected in 80% of the mesotheliomas and
6% of the adenocarcinomas. N-cadherin was expressed in 78% of
mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed
in 6% of the adenocarcinomas and in 53% of the mesotheliomas.
Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and
63% of the mesotheliomas. The results were compared with the standard
laboratory panel for mesothelioma diagnosis: anticarcinoembryonic
antigen (anti-CEA), LeuM1, BerEP4, and HBME-1. CONCLUSION: Of the
antibodies used in this study, E-cadherin was 100% sensitive for
pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary
adenocarcinoma. The application of these two antibodies alone was
adequate for the diagnosis of 69% of adenocarcinomas and 78% of
mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a
secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and
antibodies directed against CEA, calretinin, cytokeratin 5/6,
thrombomodulin, and N-cadherin, is required for differentiation between
malignant mesothelioma and pulmonary adenocarcinoma.
21
UI - 12208747
AU - Gordon GJ; Jensen RV; Hsiao LL; Gullans SR; Blumenstock JE; Ramaswamy S;
TI -
Richards WG; Sugarbaker DJ; Bueno R
Translation of microarray data into clinically relevant cancer
diagnostic tests using gene expression ratios in lung cancer and
mesothelioma.
SO - Cancer Res 2002 Sep 1;62(17):4963-7
AD - Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusetts 02115, USA.
The pathological distinction between malignant pleural mesothelioma
(MPM)and adenocarcinoma (ADCA) of the lung can be cumbersome using
established methods. We propose that a simple technique, based on the
expression levels of a small number of genes, can be useful in the early
and accurate diagnosis of MPM and lung cancer. This method is designed
to accurately distinguish between genetically disparate tissues using
gene expression ratios and rationally chosen thresholds. Here we have
tested the fidelity of ratio-based diagnosis in differentiating between
MPM and lung cancer in 181 tissue samples (31 MPM and 150 ADCA). A
training set of 32 samples (16 MPM and 16 ADCA) was used to identify
pairs of genes with highly significant, inversely correlated expression
levels to form a total of 15 diagnostic ratios using expression
profiling data. Any single ratio of the 15 examined was at least 90%
accurate in predicting diagnosis for the remaining 149 samples (e.g.,
test set). We then examined (in the test set) the accuracy of multiple
ratios combined to form a simple diagnostic tool. Using two and three
expression ratios, we found that the differential diagnoses of MPM and
lung ADCA were 95% and 99% accurate, respectively. We propose that using
gene expression ratios is an accurate and inexpensive technique with
direct clinical applicability for distinguishing between MPM and lung
cancer. Furthermore, we provide evidence suggesting that this technique
can be equally accurate in other clinical scenarios.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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