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NCI CANCERLIT® Search: Malignant Mesothelioma - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11423790
AU - Melloni G; Puglisi A; Ferraroli GM; Carretta A; Ceresoli G; Calori G;
TI -
Zannini P
[Treatment of malignant pleural mesothelioma]
SO - Minerva Chir 2001 Jun;56(3):243-50
AD - Universita Vita-Salute San Raffaele, Divisione e Cattedra di Chirurgia
Toracica, Ospedale San Raffaele, Milan, Italy.
analyzed in order to describe the impact of treatment modality on
survival. METHODS: Medical records of 56 patients with MPM (44 male, 12
female, median age = 59 yrs) were reviewed. In 34 cases the histotype
was epithelial, in 4 sarcomatoid, in 4 mixed, in 3 desmoplastic, and in
11 not specified. Four treatment modalities were identified: 1) Surgery
(subtotal pleurectomy) = 20 patients; 2) Chemotherapy = 19 patients; 3)
Surgery+Chemo-therapy = 8 patients; 4) Supportive care = 9 patients.
RESULTS: The median survival was: 1) Surgery = 12.4 months; 2)
Chemotherapy = 7.5 months; 3) Surgery+Chemotherapy = 12 months; 4)
Supportive care = 11.4 months. Using univariate analysis, 8 prognostic
factors were studied (age, sex, asbestos exposure, side, histotype,
performance status, stage, treatment). Among these, only the stage and
the performance status had shown a prognostic value on survival
(p<0.05), while the treatment modality had not significantly influenced
the prognosis. Using multivariate analysis only performance status
showed to be significatively associated with survival (p=0.01 and odds
ratio = 1.9, I.C. 1.2-3.2). CONCLUSIONS: Despite the limits of a
retrospective study, personal experience confirms the ineffectiveness of
current therapeutical approaches to MPM. A better understanding of MPM
is required to develop new therapeutical approaches and alter the dismal
prognosis of this disease.
2
UI - 11515151
AU - Merler E; Gioffre F; Rozio L; Bizzotto R; Mion M; Sarto F
TI -
[Pleural mesothelioma in women in the Veneto Region who used to work as
rag sorters for textile recycling and paper production]
SO - Med Lav 2001 May-Jun;92(3):181-6
AD - Servizio per la Prevenzione Igiene e Sicurezza nei Luoghi Lavoro, Unita
Locale Socio Sanitaria n. 16, Padova. spisal@ulss16.padova.it
The paper reports 9 cases of mesothelioma diagnosed by means of
histology or cytology that were observed among women resident in the
Veneto Region, Northern Italy, whose only activity that could involve
exposure to asbestos was as rag sorter. These cases are part of a group
of about 260 subjects with mesothelioma whose entire working and
residential history has been collected. The women worked as rag sorters
between the 1940's and 1960's in textile recycling (8 cases) or (one
case) at a paper mill where cotton was used for paper production. The
work as rag sorter helps to explain the high proportion of mesotheliomas
among women with an occupational exposure to asbestos.
3
UI - 11201579
AU - Garcia-Lopez MP; Barrera-Rodriguez R
TI -
[Malignant mesothelioma: clinical and radiological description of 45
cases with and without asbestos exposure]
SO - Salud Publica Mex 2000 Nov-Dec;42(6):511-9
AD - Instituto Nacional de Enfermedades Respiratorias, Secretaria de Salud,
Mexico.
OBJECTIVE: Our aim was to identify and describe the main symptoms,
clinical presentation, and radiographic changes in malignant
mesothelioma (MM) patients. MATERIAL AND METHODS: We reviewed the
medical and X-ray records of all patients diagnosed with MM, admitted
between 1991 and 1998 to the National Institute of Respiratory Diseases
(INER), which is a governmental institution specialized in chest disease
in Mexico City. The following data were collected: Age, occupation,
asbestos exposure, latency, family history of cancer, clinical symptoms,
and X-ray changes. Data are presented as percentages by sex and age
group. RESULTS: We found 45 cases of MM; in 80% of them a history of
asbestos exposure could not be documented. The 51-60 years age group had
the highest frequency of MM. Dispnea and chest pain were the presenting
symptoms in most patients. Pleural effusion and pleural thickening were
the X-ray abnormalities observed in 75% of the patients. CONCLUSIONS:
The clinical and radiographic findings among patients with MM without
asbestos exposure were similar to those with a history of asbestos
exposure.
4
UI - 11547584
AU - Aguilar Madrid G
TI -
[Reconstruction of the exposure to asbestos in cases of pleural
mesothelioma in Mexico]
SO - Salud Publica Mex 2001 Jul-Aug;43(4):263-5
5
UI - 11750145
AU - Metintas M; Ucgun I; Elbek O; Erginel S; Metintas S; Kolsuz M; Harmanci
TI -
E; Alatas F; Hillerdal G; Ozkan R; Kaya T
Computed tomography features in malignant pleural mesothelioma and other
commonly seen pleural diseases.
SO - Eur J Radiol 2002 Jan;41(1):1-9
AD - Department of Chest Diseases, Osmangazi University Medical Faculty,
Eskisehir, Turkey. metintas@ada.net.tr
OBJECTIVE: To investigate the computed tomography (CT) features of
malignant pleural mesothelioma (MPM) cases, comparing them to those in
other malignant and benign pleural diseases. MATERIALS AND METHODS: We
reviewed the CT findings of 215 patients; 99 with MPM, 39 with
metastatic pleural disease (MPD), and 77 with benign pleural disease.
The findings were evaluated in univariate and multivariate analysis for
differentiation of pleural diseases. RESULTS: In patients with MPM, the
most common CT features were circumferential lung encasement by multiple
nodules (28%); pleural thickening with irregular pleuropulmonary margins
(26%); and pleural thickening with superimposed nodules (20%). In the
majority (70%) of cases, there was rind-like extension of tumor on the
pleural surfaces. In multivariate analysis, the CT findings of
"rind-like pleural involvement", "mediastinal pleural involvement", and
"pleural thickness more than 1 cm" were independent findings in
differentiating MPM from MPD with the sensitivity/specificity values of
70/85, 85/67, and 59/82, respectively. "Rind-like pleural involvement",
"mediastinal pleural involvement", "pleural nodularity" and "pleural
thickness more than 1 cm" were independent findings for differentiation
of malignant pleural diseases (MPM+MPD) from benign pleural disease with
the sensitivity/specificity values of 54/95, 70/83, 38/96, and 47/64,
respectively. Invasion of thoracic structures such as pericardium, chest
wall, diaphragm, mediastinum, with pleural disease and nodular
involvement of fissures, was detected infrequently; however, since these
invasions were not seen in benign pleural diseases, it was concluded
these invasions, if detected on a CT scan, directly suggested
malignancy. CONCLUSION: A patient has extremely high probability of
malignant pleural disease if one or more of these CT findings are found
and the possibility of MPM is high. These findings may be important for
patients in bad state or patients who do not want any invasive biopsy
procedures. It is also possible to identify cases with a low probability
of malignant disease.
6
UI - 11846639
AU - Walker AM; Maxim LD; Utell M
TI -
Risk analysis for mortality from respiratory tumors in a cohort of
refractory ceramic fiber workers.
SO - Regul Toxicol Pharmacol 2002 Feb;35(1):95-104
AD - Epidemiology Division, Ingenix Pharmaceutical Services, One Newton
Executive Park, Newton Lower Falls, Massachusetts 02462-9669, USA.
AlecWalker@Epidemiology.com
Although workers in refractory ceramic fibers (RCF) manufacturing
facilities have experienced no elevations in lung cancer or mesothelioma
rates, the historical experience of asbestos together with animal
studies of RCF have led to ongoing studies of the respiratory health of
RCF workers. We have compared lung cancer and mesothelioma in the
accumulated mortality experience of a cohort of male RCF production
workers (Lemasters et al., 2001, submitted for publication) to that
which would have been expected if RCF had a carcinogenic potency similar
to that of various forms of asbestos. To accomplish this, we used risk
models recently formalized by Hodgson and Darnton (2000, Ann. Occup.
Hyg. 41, 13-36) for asbestos cohorts together with the RCF exposure
measurements and historical reconstructions of Rice and colleagues
(1997, Appl. Occup. Environ. Hyg. 12, 54-61). Deaths from lung cancer in
the RCF cohort are statistically significantly below that which would be
expected if RCF had the potency of either crocidolite or amosite. The
mortality is also lower than would be expected if RCF had the potency of
chrysotile, but the difference is not statistically significant. For
mesothelioma, the anticipated numbers of deaths under hypotheses of
asbestos-like potency are too small to be rejected by the zero cases
seen in the RCF cohorts. The current epidemiologic studies do not rule
out risk, but they clearly do rule out lung cancer risks like those of
crocidolite or amosite. The residual uncertainty justifies ongoing
workplace surveillance. B) 2002 Elsevier Science (USA).
7
UI - 11862420
AU - Bright RK; Kimchi ET; Shearer MH; Kennedy RC; Pass HI
TI -
SV40 Tag-specific cytotoxic T lymphocytes generated from the peripheral
blood of malignant pleural mesothelioma patients.
SO - Cancer Immunol Immunother 2002 Feb;50(12):682-90
AD - Laboratory of Prostate Cancer Biology, Robert W. Franz Cancer Research
Center, Earle A. Chiles Research Institute, and the Oregon Cancer
Center, 4805 NE Glisan Street, Portland, OR 97213, USA.
rbright@providence.org
Malignant pleural mesothelioma (MPM) is an aggressive cancer, with
survival of less than one year following diagnosis and treatment with
current protocols. Recent studies have demonstrated the presence of the
simian virus 40 (SV40)-like, large tumor antigen (Tag) in nearly 60% of
MPMs. SV40 Tag is a viral-encoded tumor-specific antigen, and thus a
potential target for the induction of anti-tumor immunity and the
development of therapeutic vaccines. We describe here evidence for the
existence of SV40 Tag-specific immune responses in patients with MPM
whose tumors express Tag. Humoral immunity was demonstrated by the
detection of IgG titers against Tag in serum samples from 1/3 of
patients examined. CTLs were generated from the peripheral blood of an
HLA-A2(+) MPM patient with a synthetic peptide representing an HLA-A2
binding epitope in SV40 Tag. The CTLs demonstrated epitope fine
specificity, in that other peptides from SV40 Tag and a peptide from
influenza virus were not recognized in the context of HLA-A2. Moreover,
the CTLs were capable of recognizing mesothelioma tumor cells that
expressed SV40 Tag, in an MHC class I restricted manner.
8
UI - 11905410
AU - Kerrigan SA; Turnnir RT; Clement PB; Young RH; Churg A
TI -
Diffuse malignant epithelial mesotheliomas of the peritoneum in women: a
clinicopathologic study of 25 patients.
SO - Cancer 2002 Jan 15;94(2):378-85
AD - Department of Pathology, Vancouver Hospital and Health Sciences Center,
British Columbia, Canada.
BACKGROUND: The behavior of diffuse peritoneal mesotheliomas in women
and the possible relation between tumor morphology and outcome are
uncertain. Reported survival has ranged from < 1 month to > 14 years,
and a previous study found that tumor morphology could not be used
reliably for predicting outcome. The authors examined the behavior of
diffuse epithelial peritoneal mesotheliomas in women and the possible
relation between pathologic features and outcome. METHODS: Twenty-five
female patients with diffuse peritoneal epithelial malignant
mesotheliomas were divided into two groups: those who survived for < 4
years (60%) and those who survived for > 4 years (40%). Both groups were
compared in terms of age, presentation, treatment, survival, tumor
architecture, mitotic rate, necrosis, nuclear grade, and
immunohistochemical profile. RESULTS: Patients in the two groups were
similar in terms of age at diagnosis (median ages, 50.7 years and 49.9
years), presentation, initial tumor burden, and treatment. In both
groups, the most common initial clinical presenting features were
ascites and abdominal pain. The tumors typically took the form of
multiple nodules measuring < 1.5 cm in greatest dimension. Slightly less
than 50% of patients in both groups received some form of chemotherapy
or radiation therapy after undergoing tumor-reductive surgery or biopsy.
Overall survival ranged from 1 month to 15 years. The median survival
was 12 months in the group of women who survived for < 4 years and 7
years in the group of women who survived for > 4 years. Overall, 10 of
25 patients survived for > or = 5 years. One patient was alive with
disease 15 years after diagnosis. Although there was a suggestion that
the tumors in patients with short survival more often had solid
architecture and high-grade nuclei, these findings were not significant
statistically. The frequency of necrosis and the mitotic activity were
the same in both groups. CONCLUSIONS: The spectrum of diffuse epithelial
peritoneal mesotheliomas in women includes tumors that are highly
aggressive and behave much like pleural mesotheliomas, although a
sizeable number of tumors, unlike the pleural tumors, are relatively
indolent. However, because there do not appear to be morphologic
features that reliably identify favorable tumors versus unfavorable
tumors, aggressive therapy for all women with diffuse peritoneal
mesotheliomas may be warranted.
9
UI - 11875694
AU - Mendes R; O'Brien ME; Mitra A; Norton A; Gregory RK; Padhani AR;
TI -
Bromelow KV; Winkley AR; Ashley S; Smith IE; Souberbielle BE
Clinical and immunological assessment of Mycobacterium vaccae (SRL172)
with chemotherapy in patients with malignant mesothelioma.
SO - Br J Cancer 2002 Feb 1;86(3):336-41
AD - Lung Unit, Department of Haematology, The Royal Marsden Hospital NHS
Trust, Downs Road, Sutton, SM2 5PT, UK.
The objectives of this study were to determine the toxicity of
intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and
standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in
patients with malignant mesothelioma. Patients received chemotherapy
(mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg
m(-2)) on a 3-weekly basis for up to six courses. IP SRL172 injections
were given 3-weekly prior to chemotherapy and escalated in groups of
three patients from 1 microg to 1 mg bacilli in 10-fold increments.
Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly.
Patients were assessed for toxicity after each course of chemotherapy
and for response by CT imaging. Immuno-haematological parameters were
analyzed pre-treatment and 1 month after completion of treatment. There
was no dose limiting toxicity with IP SRL172 although there was greater
toxicity at the highest dose (n=13). There were six out of 16 partial
responses (37.5%). Haemato-immunological parameters, measured in seven
patients pre and post-therapy, revealed that response rate correlated
with a decrease in platelet count and there was an increase in
activation of natural killer cells and a decrease in the percentage of
IL-4 producing T cells in all tested patients post-treatment. SRL172 can
be given safely into tumour deposits and the pleural cavity in patients
with malignant mesothelioma and we have established the dose for phase
II testing. Copyright 2002 The Cancer Research Campaign
10
UI - 11875695
AU - van Haarst JM; Baas P; Manegold Ch; Schouwink JH; Burgers JA; de Bruin
TI -
HG; Mooi WJ; van Klaveren RJ; de Jonge MJ; van Meerbeeck JP
Multicentre phase II study of gemcitabine and cisplatin in malignant
pleural mesothelioma.
SO - Br J Cancer 2002 Feb 1;86(3):342-5
AD - Rotterdam Oncological Thoracic Studygroup (ROTS), Department of
Pulmonology, University Hospital Rotterdam, PO Box 5201, 3008 AE
Rotterdam, The Netherlands.
Malignant pleural mesothelioma is a notoriously chemoresistant tumour.
However, a recent single institution study showed an impressive activity
of gemcitabine and cisplatin. Our aim is to investigate the efficacy and
toxicity of a gemcitabine and cisplatin combination in selected and
chemo-naive patients with histologically proven malignant pleural
mesothelioma. METHOD: Gemcitabine 1250 mg m(-2) was administered on day
1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a
3-week cycle with a maximum of six cycles. Response and toxicity
evaluations were performed according to WHO and NCIC-CTC criteria.
Pathology and radiology were centrally reviewed. Results show that in 25
evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%).
Responses of seven patients were unevaluable. No unexpected toxicity
occurred. Time to progression was 6 months (5-7 months) with a median
survival from registration of 9.6 months (95% CI 8-12 months). In
conclusion this trial excludes with 90% power a response rate of greater
than 30% in patients with malignant pleural mesothelioma using a
combination of gemcitabine and cisplatin at the proposed dose and
schedule. Copyright 2002 The Cancer Research Campaign
11
UI - 11924240
AU - Riviere A
TI -
[Does treatment for malignant pleural mesothelioma exist?]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S3-6
AD - CLCC Francois Baclesse, Caen.
12
UI - 11895489
AU - Attanoos RL; Webb R; Dojcinov SD; Gibbs AR
TI -
Value of mesothelial and epithelial antibodies in distinguishing diffuse
peritoneal mesothelioma in females from serous papillary carcinoma of
the ovary and peritoneum.
SO - Histopathology 2002 Mar;40(3):237-44
AD - Department of Histopathology, Llandough Hospital, Cardiff & Vale NHS
Trust, Penarth, Vale of Glamoran, UK.
AIMS: To evaluate the role of mesothelial markers (calretinin,
thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers
(polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and
Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma
from primary serous papillary adenocarcinoma of the ovary and
peritoneum. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks
from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all
females), 20 serous papillary ovarian carcinomas and three primary
peritoneal serous papillary carcinomas were studied. Calretinin and
Ber-EP4 appeared to be the best positive mesothelial and carcinoma
marker, respectively. Nuclear calretinin expression was identified in 28
of 32 malignant mesotheliomas with no nuclear immunoreactivity in the
cohorts of serous papillary ovarian and peritoneal carcinomas, thus
yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95%
sensitivity and 91% specificity for serous papillary ovarian carcinoma.
Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen
in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas,
respectively, and in six (30%), five (25%) and five (25%) of the ovarian
tumours, respectively. None of the three primary peritoneal serous
papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin
5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed
by two (10%), one (5%) and seven (35%) serous papillary ovarian
carcinomas, respectively. None of the serous papillary peritoneal
carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125
was positive in 19 (95%) and two (67%) ovarian and peritoneal
carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas.
CONCLUSIONS: Calretinin and Ber-EP4 are useful discriminant markers in
distinguishing peritoneal mesothelioma in women from serous papillary
ovarian and peritoneal carcinoma. The other mesothelial markers
(thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers
(polyclonal and monoclonal CEA, and Leu-M1) yielded a too low
sensitivity for practical use.
13
UI - 11828056
AU - Robinson M; Wiggins J
TI -
Statement on malignant mesothelioma in the UK.
SO - Thorax 2002 Feb;57(2):187
14
UI - 11828058
AU - Rudd R; Moore-Gillon J; Muers M
TI -
Mesothelioma.
SO - Thorax 2002 Feb;57(2):187
15
UI - 11862475
AU - Ehlers EM; Kuhnel W; Wiedemann GJ
TI -
Hyperthermia and mafosfamide in a human-derived malignant pleural
mesothelioma cell line.
SO - J Cancer Res Clin Oncol 2002 Feb;128(2):65-72
AD - Department of Anatomy, Medical University of Lubeck, Lubeck, Germany.
ehlers@anat.mu-luebeck.de
PURPOSE: Diffuse malignant pleural mesothelioma is the most common
primary pleural malignancy. At the beginning of the last century, this
tumor was of minor incidence. Meanwhile, the use of asbestos has led to
and is still leading to a rise in pleural mesothelioma incidence. There
is no standard therapy for this highly aggressive disease and the
development of new therapeutic strategies is imperative. METHODS: We,
therefore, investigated the morphological and pharmakokinetic effects of
a combined thermochemotherapy consisting of the administration of
different dosages of mafosfamide with and without the application of a
1-h hyperthermia at 41.7 degrees C on the human biphasic malignant
pleural mesothelioma cell line MSTO-211H. After therapy, cells were
prepared for light and electron microscopy. BrdU-incorporation for the
S-phase fraction, TUNEL-labeling for detection of apoptosis, and
quantitative assessments using the MTT assay were performed. RESULTS:
Our results demonstrate that the combination of mafosfamide with
hyperthermia leads to qualitatively and quantitatively enhanced cellular
damage compared to monotherapy. During combined thermochemotherapy, cell
damage and death is already induced at lower mafosfamide concentrations
than without hyperthermia which suggests an additive effect from
hyperthermia to the action of the alkylating drug mafosfamide. Cell
death thereby mostly occurs as necrotic cell death rather than as
apoptosis, although in a combined thermochemotherapy apoptosis is
induced temperature-dependently, when comparing temperatures from 37
degrees C to 43 degrees C. CONCLUSIONS: We suggest that the effect of
substances such as ifosfamide and cyclophosfamide which are in clinical
use, might be enhanced by the combination of local or regional
hyperthermia in order to improve the therapeutical index of these
substances in the treatment of pleural mesothelioma.
16
UI - 11933737
AU - Letonturier P
TI -
[Malignant pleural mesothelioma. A rare tumor that has become a
world-wide public health problem]
SO - Presse Med 2002 Mar 9;31(9):405
17
UI - 11933738
AU - Bard M; Ruffie P
TI -
[Malignant pleural mesothelioma. From diagnosis to prognosis]
SO - Presse Med 2002 Mar 9;31(9):406-11
AD - Institut Gustave-Roussy, Departement de Medecine, 39, rue Camille
Desmoulins, F94805 Villejuif.
EPIDEMIOLOGY: The incidence of malignant pleural mesothelioma has
constantly increased over the past forty years. The recent measures of
ban on the use of asbestos and the long latency of this tumor after
exposure means that its peak incidence can be foreseen for the years
2010-2020. DIAGNOSIS: Various health professionals are involved in the
care of this tumor, which benefits equally from progresses in clinical
and fundamental research. Some progress has been made in understanding
its oncogenesis as well as its histopathologic analysis. PROGNOSIS:
Malignant pleural mesothelioma symptoms are rapidly invalidating and the
patient's prognosis is bad at short-term. However, hope may come from
the detection of early stages of the disease and from the
individualization of good prognosis factors, permitting the selection of
patients for whom some curative therapies are in course of evaluation.
18
UI - 11933739
AU - Bard M; Ruffie P
TI -
[Malignant pleural mesothelioma. Present data and perspectives for
treatment]
SO - Presse Med 2002 Mar 9;31(9):412-9
AD - Institut Gustave-Roussy, Departement de Medecine, 39, rue Camille
Desmoulins, F94805 Villejuif.
CHEMOTHERAPY: With regard to the efficacy of mono-chemotherapy and
according to the literature, no cytotoxic substance, apart from
methrotrexate at high doses, leads to a response rate of more than 20%.
With regard to cyrotoxic associations, the published results show
slightly betterresponse rates. IMMUNOTHERAPY: Interleukine 2 as well as
various interferons have been tested alone or in association with
chemotherapy. Fairly encouraging response rates have been reported.
However, the possibility of severe adverse events must be taken into
account. RADIOTHERAPY: The interest of prophylactic parietal radiation
following invasive thoracic treatment has been demonstrated. Palliative
use of radiotherapy is possible for pain, and more rarely for
decompression. With curative aim, the results of isolated radiotherapy
are disappointing. SURGERY: Palliative surgery is aimed at reducing the
tumour and pleural symphysis. Curative surgery consists in wide
extrapleural pneumonectomy, permitting total resection of the visceral
pleura, or decortication pleurectomy leaving the lung in place. Mean
survival of patients having undergone surgery is of 10 to 17 months with
rates between 10 and 30% at 2 years ASSOCIATED THERAPY: For the first
time, despite high morbidity rates, associated therapy has led to
prolonged survival, whereas isolated therapy has not. This is the case
with an association of radical surgery, radiotherapy and adjuvant
chemotherapy. IN THE FUTURE: In the treatment of malignant pleural
mesothelioma, genetic, anti-proliferative and immune therapy, that
attempt to use the immune system of the patient to obtain an anti-tumour
cytotoxic reaction, appear promising.
19
UI - 10598561
AU - Thodtmann R; Depenbrock H; Blatter J; Johnson RD; van Oosterom A;
TI -
Hanauske AR
Preliminary results of a phase I study with MTA (LY231514) in
combination with cisplatin in patients with solid tumors.
SO - Semin Oncol 1999 Apr;26(2 Suppl 6):89-93
AD - Universitair Ziekenhuis Gasthuisberg, Katholic University of Leuven,
Belgium.
MTA (multitargeted antifolate, LY231514) is a novel antimetabolite
resulting from structure/activity studies of the lometrexol-type
antifolates. It has been shown to inhibit various enzymes of folate
pathways and has broad antitumor activity in a variety of in vitro and
in vivo tumor models. Clinical phase 1 studies have been performed using
different administration schedules, and subsequently the every-21-days
schedule has been selected for further development. We report the
preliminary findings from a combination phase I study of MTA and
cisplatin administered every 21 days. In the first cohort (34 patients),
both agents were administered on day 1 with a starting dose of 300 mg/m2
MTA and 60 mg/m2 cisplatin. In a second cohort (10 patients), MTA (500
or 600 mg/m2) was administered on day 1 followed by cisplatin (75 mg/m2)
on day 2. The maximum tolerated doses were reached at 600 mg/m2 MTA/100
mg/m2 cisplatin (cohort 1) and 600 mg/m2 MTA/75 mg/m2 cisplatin (cohort
2). In cohort 1, dose-limiting toxicities consisted of reversible
myelosuppression with leukopenia and neutropenia. In addition, delayed
fatigue also was of clinical significance. Pharmacokinetic analyses
indicated that hydration administered before the administration of
cisplatin did not influence the major pharmacokinetic parameters of MTA.
Eleven objective remissions were observed, including one complete
response in a patient with relapsed squamous cell carcinoma of the head
and neck and partial responses in four of seven patients with
mesothelioma In contrast, the dose-limiting toxicities in patient cohort
2 consisted of neutropenic sepsis, diarrhea, and skin toxicity with two
possibly treatment-related deaths on study. No objective remissions are
presently observed in cohort 2. We conclude that the combination of MTA
and cisplatin is feasible and clinically active when both agents are
administered on day 1 and that it should be pursued for further clinical
development.
20
UI - 10640996
AU - Dhaene K; Wauters J; Weyn B; Timmermans JP; van Marck E
TI -
Expression profile of telomerase subunits in human pleural mesothelioma.
SO - J Pathol 2000 Jan;190(1):80-5
AD - Laboratory of Pathology, University of Antwerp (UIA), Department of
Medicine, Universiteitsplein 1, B-2610 Wilrijk - Antwerp, Belgium.
Using the TRAP assay, telomerase activity was previously detected in
over 90% of human pleural mesotheliomas (MMs), but not in mesothelial
cell cultures (MCCs), suggesting that telomerase re-activation occurs
during multi-step mesothelioma carcinogenesis. The present study
determined the expression of the telomerase RNA template (hTERC), the
telomerase-associated protein (hTEP1), and the telomerase catalytic
sub-unit (hTERT), in 16 pleural MMs and 4 MM-derived cell lines, in two
pleural solitary fibrous tumours and in six MCCs. Reverse
transcription-polymerase chain reaction analysis revealed that hTERT
mRNA expression parallels the activity status documented by the TRAP
assay, whereas hTERC and hTEP1 mRNA are commonly expressed in all
malignant and non-malignant serosal cells and tissues. Three
alternatively spliced hTERT transcripts were detected in all
telomerase-positive samples, whereas neither variant could be detected
in the MCCs. Detection of the hTERT protein with a commercially
available antibody was not successful. These results indicate that hTERT
expression is rate-limiting for human telomerase activity and that
re-activation, rather than up-regulation, of hTERT expression can play a
critical role in MM carcinogenesis. While waiting suitable anti-hTERT
antibodies, these results provide information for the design of hTERT
mRNA-specific in situ probes to study telomerase in archived
pre-malignant serosal lesions. Copyright 2000 John Wiley & Sons, Ltd.
21
UI - 11903576
AU - Attanoos RL; Webb R; Dojcinov SD; Gibbs AR
TI -
Malignant epithelioid mesothelioma: anti-mesothelial marker expression
correlates with histological pattern.
SO - Histopathology 2001 Dec;39(6):584-8
AD - Department of Histopathology, Llandough Hospital, Cardiff and Vale NHS
Trust, Penarth, Wales, UK.
AIMS: Malignant epithelioid mesothelioma shows marked cytoarchitectural
diversity. The aim of the study was to evaluate how immunoreactivity
with mesothelial markers related to histological pattern. METHODS AND
RESULTS: Ninety-two cases of malignant epithelioid mesothelioma (60
pleural, 32 peritoneal) were examined and classified as exhibiting
tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns.
All cases were immunohistochemically stained with thrombomodulin,
calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma
exhibited a number of different histological forms. Immunohistochemical
expression of each mesothelial marker tested was not homogeneous across
different histological patterns of malignant epithelioid mesothelioma,
even within the same tumour section. Calretinin (with nuclear
expression) was identified to show the highest overall sensitivity and
lowest range variation in staining (67% sensitivity in small cell areas
to 100% expression in pleomorphic areas). Cytokeratin 5/6 and
thrombomodulin yielded similar overall sensitivity. Thrombomodulin
appeared to demonstrate higher sensitivity for small cell variant tumour
(83% sensitivity). A notable advantage with cytokeratin 5/6 was that
expression was more diffuse in nature rather than the focal membranous
elaboration seen in thrombomodulin. The widest range of staining was
seen in small cell mesothelioma (83% sensitivity with thrombomodulin to
17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90%
sensitivity with calretinin to 38% sensitivity with CD44H). CONCLUSIONS:
Calretinin appears most useful and shows the highest overall sensitivity
for malignant epithelioid mesothelioma, with good expression in areas
displaying a tubulopapillary, adenomatoid, solid and pleomorphic
pattern. For small cell mesothelioma, thrombomodulin appears to confer
higher sensitivity and is advocated, in this setting, as the first line
mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable
mesothelial marker. CD44H is not of particular use in the diagnosis of
malignant epithelioid mesothelioma. Accurate interpretation of
immunohistochemistry in mesothelioma requires an awareness of the
immunophenotypic heterogeneity identified in different histological
forms of the tumour, and this is of particular importance in small
biopsies.
22
UI - 11903583
AU - Bishop PW
TI -
Panel for distinction between mesothelioma and adenocarcinoma:
confidence limits for a small study.
SO - Histopathology 2001 Dec;39(6):639-40
23
UI - 11920963
AU - Leigh J; Davidson P; Hendrie L; Berry D
TI -
Malignant mesothelioma in Australia, 1945-2000.
SO - Am J Ind Med 2002 Mar;41(3):188-201
AD - Center for Occupational and Environmental Health, Department of Public
Health and Community Medicine, University of Sydney, Sydney, NSW,
Australia. jleigh@bigpond.com
BACKGROUND: Australia has maintained a total national malignant
mesothelioma case register since 1980. There has been a marked increase
in the incidence of mesothelioma in the last 20 years. Currently 450-600
cases are notified annually in a population of 20 million. While the
history of the Wittenoom (Western Australia) crocidolite mine and its
aftermath is well known, these cases comprise only 5% of the total. This
study describes the incidence of mesothelioma in Australia from 1945 to
2000. METHODS: Using register data, time trends in mesothelioma
incidence were calculated. Analyses of incidence are reported by age,
sex, anatomical site, and state of notification. Associations with
occupational and environmental asbestos exposure histories are
described. Lung fiber content measurements were made on a subset of
cases. RESULTS: Australia has had 6,329 cases of mesothelioma from 1
rates for Australia per million population > or = 20 years (1997) were:
male, 59.8; female, 10.9; total, 35.4. Incidence rates have been
continually increasing and are the highest reported national rates in
the world. While Western Australia has the highest rate (1997 total
rate, 52.8), most cases arise from the two most populous eastern states,
New South Wales and Victoria. In 88% (male 90%, female 61%) of cases, a
history of asbestos exposure was obtained. Exposures occurred in a wide
variety of occupational and environmental circumstances. In 80% of cases
with no history of exposure, TEM lung asbestos fiber counts > 200,000
fibers > 2 microm length per gm dry lung were obtained, suggesting
unrecognized exposure. CONCLUSIONS: Australia's high incidence of
mesothelioma is related to high past asbestos use, of all fiber types,
in a wide variety of occupational and environmental settings. The number
of cases in total is expected to be about 18,000 by 2020, with about
11,000 yet to appear. Copyright 2002 Wiley-Liss, Inc.
24
UI - 11911261
AU - Horita K; Inase N; Miyake S; Formby B; Toyoda H; Yoshizawa Y
TI -
Progesterone induces apoptosis in malignant mesothelioma cells.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3871-4
AD - The Pulmonary Medicine, Tokyo Medical and Dental University, Japan.
Progesterone has been used in the treatment of patients with recurrent
or metastatic progesterone receptor-positive endometrial carcinoma and
breast cancer. In vitro study using a breast cancer cell line, T47D,
demonstrated an increase in p53 gene expression and induction of
apoptosis by the administration of progesterone. Therefore, we
investigated the effect of progesterone administration on the
proliferation and apoptosis in a mesothelioma cell line, 211H. The
expression of the progesterone receptor gene was detected in this cell
line by a nested RT-PCR method. The proliferation of the cell line was
suppressed after a 10-day incubation with 30 microM progesterone. In
progesterone-treated 211H cells, apoptotic cells were detected by TUNEL
assay and nuclear DNA fragmentation analysis. These results clearly
demonstrated that progesterone administration suppressed the cell
proliferation and induced apoptosis in malignant mesothelioma cells.
25
UI - 10976692
AU - Churg A; Colby TV; Cagle P; Corson J; Gibbs AR; Gilks B; Grimes M;
TI -
Hammar S; Roggli V; Travis WD
The separation of benign and malignant mesothelial proliferations.
SO - Am J Surg Pathol 2000 Sep;24(9):1183-200
AD - University of British Columbia, Vancouver, BC, Canada.
achurg@interchange.ubc.ca
The separation of benign from malignant mesothelial proliferations has
emerged as a major problem in the pathology of the serosal membranes.
For both epithelial and spindle cell mesothelial processes, true stromal
invasion is the most accurate indicator of malignancy, but stromal
invasion is often difficult to assess, especially in small biopsies. In
the pleural cavity, deep penetration of a thickened and fibrotic pleura
or penetration of mesothelial cells into the fat of the chest wall are
good indicators of malignancy; however, superficial entrapment of
mesothelial cells and glands by organizing effusions is common in benign
reactions and needs to be distinguished from invasion. In the peritoneal
cavity, invasion of fat or of organ walls is again the most reliable
indicator of malignancy, but entrapment of benign cells in organizing
granulation tissue or between fat lobules is frequent and confusing.
Proliferations confined to the pleural or peritoneal space, particularly
linear arrays of atypical mesothelial cells on the free surface, should
not be called malignant in the absence of unequivocal invasion.
Cytologic atypia is often not helpful in separating benign from
malignant reactions, because benign processes are commonly atypical and
mesotheliomas are often deceptively monotonous. Densely packed
mesothelial cells within the pleural space are frequent in benign
reactions, but densely packed mesothelial cells within the stroma favor
a diagnosis of malignancy. Organizing effusions (fibrous pleurisy)
typically show zonation with high cellularity and cytologic atypia
toward the pleural space and increasing fibrosis with decreasing
cellularity and lesser atypia toward the chest wall, whereas sarcomatous
(including desmoplastic) mesotheliomas do not demonstrate this type of
zonation. Elongated capillaries perpendicular to the pleural surface are
seen in organizing effusions but are not a feature of sarcomatous
mesotheliomas. The combination of a paucicellular storiform pattern,
plus invasion of the stroma (including fat and adjacent tissues), or
bland necrosis, overtly sarcomatous foci, or distant metastases, is
required for the diagnosis of desmoplastic mesothelioma. Necrosis is
usually a sign of malignancy but is occasionally seen in benign
mesothelial reactions. Keratin staining is useful in indicating the
distribution of mesothelial cells, and particularly in demonstrating
penetration of mesothelial cells into the stroma or adjacent structures,
but is of no help in separating benign and malignant proliferations
because both are keratin-positive. Although both p53 and EMA staining
have been proposed as markers of mesothelial malignancy, in our
experience they are not helpful for the individual case.
26
UI - 11257637
AU - Koss LG
TI -
Benign and malignant mesothelial proliferations.
SO - Am J Surg Pathol 2001 Apr;25(4):548-9
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