Table of Contents
1
UI - 21230216
AU - Diaz-Ruiz C; Montaner B; Perez-Tomas R
TI -
Prodigiosin induces cell death and morphological changes indicative of
apoptosis in gastric cancer cell line HGT-1.
SO - Histol Histopathol 2001 Apr;16(2):415-21
AD - Department of Cell Biology and Pathology, University of Barcelona,
L'Hospitalet, Spain.
Gastric cancer is one of the most frequent malignancies and its
treatment is far from satisfactory. The challenge to oncologists is the
characterization of novel chemical entities with greater effectiveness.
Prodigiosin is a red pigment produced by various bacteria including
Serratia marcescens. Here we characterize the apoptotic action of
prodigiosin in human gastric carcinoma cell line (HGT-1). Cells were
assayed by the MTT assay, fragmentation pattern of DNA, Hoechst 33342
staining and study of actin microfilament architecture. Treatment of
these cells with prodigiosin showed a constant decrease in viability by
apoptosis. Morphological analysis of prodigiosin-treated cells
demonstrated that prodigiosin induces cell shrinkage, chromatin
condensation, reorganization of actin microfilament architecture, and
detachment of cells from the cell culture substrate. Altogether these
results suggest that prodigiosin induces apoptosis in HGT-1 human
gastric cancer cells and raises the possibility of its use as a new
chemotherapeutic drug.
2
UI - 21256509
AU - Lee KH; Lee JH; Cho JK; Kim TW; Kang YK; Lee JS; Kim WK; Chung JG; Lee
TI -
IC; Sun HS
A prospective correlation of Lauren's histological classification of
stomach cancer with clinicopathological findings including DNA flow
cytometry.
SO - Pathol Res Pract 2001;197(4):223-9
AD - Department of Medicine, University of Ulsan, College of Medicine, Asan
Medical Center, Seoul, Korea. khlee2@www.amc.seoul.kr
cancer were enrolled in a prospective study evaluating the prognostic
value of DNA flow cytometry. Lauren's histological type was evaluated in
216 cases, of which 102 (47%) were of the diffuse type, 74 (34%) were of
the intestinal type, and 40 (19%) were mixed type tumors. Lauren's
histological type showed a significant correlation with age (p = 0.028),
sex (p = 0.004), tumor size (p = 0.002), T stage (p = 0.006), overall
TNM stage (p = 0.008), histological grade (p < 0.001), and tumor ploidy
(p < 0.001). Intestinal type stomach cancer showed a significantly
higher proportion of aneuploidy [diffuse vs. intestinal type; 41/102
(40%) vs. 52/74 (70%)]. After a median follow-up of 66.1 months (range,
29.6-78.1), 110 of 216 patients (51%) survived. Patients with intestinal
type stomach cancer had a significantly better survival than did those
with diffuse type stomach cancer (64% vs. 42% of patients surviving, p =
0.020). Our study suggests that there are biological differences between
the two subtypes of Lauren's classification of stomach cancer in
addition to the morphological differences. Lauren's classification
should remain valid in future studies investigating the pathogenetic and
clinical aspects of stomach cancer.
3
UI - 21274954
AU - Park RM
TI -
Mortality at an automotive engine foundry and machining complex.
SO - J Occup Environ Med 2001 May;43(5):483-93
AD - Risk Evaluation Branch, Education and Information Division, National
Institute for Occupational Safety and Health, 4676 Columbia Parkway,
Cincinnati, OH 45226-1998, USA.
Mortality was analyzed for an automotive engine foundry and machining
complex, with process exposures derived from department assignments.
Logistic regression models of mortality odds ratios (ORs) were
calculated for 2546 deaths, and numbers of work-related deaths were
estimated. Lung cancer mortality in the foundry was increased where
cleaning and finishing of castings was performed (OR, 1.7; 95% CI, 1.15
to 2.4 [at mean exposure duration of exposed cases]) and in care-making
after 1967 (OR, 1.5; 95% CI, 1.11 to 2.0). Black workers had excess lung
cancer mortality in machining heat-treat operations (OR, 2.5, 95% CI,
1.4 to 4.3) and excess nonmalignant respiratory disease mortality in
molding (OR, 2.5; 95% CI, 1.16 to 5.5) and core-making (OR, 2.7; 95% CI,
1.25 to 5.8). Stomach cancer mortality was elevated among workers with
metalworking fluid exposures in precision grinding (OR, 2.4; 95% CI,
1.14 to 5.1). Heart disease mortality was increased among all workers in
molding (OR, 1.6; 95% CI, 1.09 to 2.3), as was stroke mortality among
workers exposed to metalworking fluids (OR, 1.8; 95% CI, 1.22 to 2.7).
Malignant and nonmalignant liver disease mortality was elevated in
assembly/testing and precision grinding. In this modern foundry, 11% of
deaths were estimated to be work-related despite it's being largely in
regulatory compliance over its 40-year existence. Machining plant
exposures accounted for 3% or more of deaths there.
4
UI - 21338539
AU - Saitoh T; Katoh M
TI -
FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are
up-regulated in gastric cancer.
SO - Int J Oncol 2001 Aug;19(2):311-5
AD - Genetics and Cell Biology Section, Genetics Division, National Cancer
Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Japan.
FRAT1 and FRAT2 are cancer-associated genes encoding GSK-3beta-binding
proteins. Over-expression of FRAT1 or FRAT2 lead to carcinogenesis
through activation of WNT--beta-catenin--TCF signaling pathway. We have
previously cloned and characterized FRAT2. Here, we found that FRAT1 and
FRAT2 genes were clustered in the human chromosome 10q24.1 region. Blast
search revealed that FRAT1 and FRAT2 genes, consisting of a single exon,
were located together on human genome draft sequences AC006098.1 and
AL355490.7, corresponding to the human chromosome 10q24.1 region. FRAT1
and FRAT2 genes were clustered in a tail to tail manner with an interval
of about 10.7 kb. The 2.7-kb FRAT1 mRNA was relatively highly expressed
in fetal brain, adult spleen, pancreas, HeLa S3 (cervical cancer), and
K-562 (chronic myelogenous leukemia). FRAT1 and FRAT2 were co-expressed
in 7 gastric cancer cell lines and 10 cases of primary gastric cancer,
and were up-regulated together in gastric cancer cell line TMK1 and 2
cases of primary gastric cancer. These results indicated that FRAT1 and
FRAT2 genes were up-regulated together in several cases of human gastric
cancer. Up-regulation of FRAT1 and FRAT2 in gastric cancer might lead to
carcinogenesis through activation of WNT--beta-catenin--TCF signaling
pathway.
5
UI - 21338549
AU - Yukimoto K; Nakata B; Muguruma K; Yashiro M; Ohira M; Ishikawa T; Hino
TI -
M; Hirakawa K
Apoptosis and thymidylate synthase inductions by 5-fluorouracil in
gastric cancer cells with or without p53 mutation.
SO - Int J Oncol 2001 Aug;19(2):373-8
AD - Department of Surgical Oncology (First Department of Surgery), Osaka
City University Graduate School of Medicine, 1-4-3 Asahi-machi,
Abeno-ku, Osaka 545-8585, Japan.
We studied apoptosis and thymidylate synthase (TS) inductions by
5-fluorouracil (5-FU) in gastric cancer cells with wild-type p53 (MKN-45
and MKN-74) and with mutated p53 (MKN-28 and KATO-III). Apoptotic
inductions in MKN-45 and MKN-74 were stronger than those in MKN-28 and
KATO-III, suggesting that wild-type p53 may contribute to the induction
of apoptosis. After continuous exposure to 0.1 microg/ml of 5-FU for 96
h, no TS induction was obtained in KATO-III, while approximately twice
the amount of TS was observed compared to non-treatment cells in MKN-45,
MKN-74, and MKN-28. The results of immunohistochemical staining for TS
and p53 showed no relation between these two protein expressions in
endoscopic biopsy specimens of 25 patients with advanced gastric cancer.
These results indicated that p53 status may not play a pivotal role in
regulating TS expression. We found no significantly different effects of
5-FU between intermittent (repeat of 24-h continuous infusion and 24-h
drug-free) and continuous treatments in either MKN-28 or stem cells
(CD34+ hematopoietic progenitor cells) when the same area under the
time-concentration curve of 5-FU was administered. The TS induction in
MKN-28 cells by intermittent treatment was significantly higher than
that by continuous treatment; however, most TSs in both types of 5-FU
treatment cells were of the inactive form, i.e., TS bound to FdUMP, a
5-FU metabolite. Therefore, neither intermittent nor continuous
treatment appears to induce 5-FU resistance related to the level of
increment free TS. In conclusion, our observations suggested that p53
mutation may be associated with apoptotic induction by 5-FU; however,
p53 status may not strongly affect TS induction by 5-FU. Intermittent
treatment can be replaced with continuous treatment without causing 5-FU
resistance.
6
UI - 21353204
AU - Thong-Ngam D; Tangkijvanich P; Mahachai V; Kullavanijaya P
TI -
Current status of gastric cancer in Thai patients.
SO - J Med Assoc Thai 2001 Apr;84(4):475-82
AD - Department of Physiology, King Chulalongkorn Memorial Hospital, Bangkok,
Thailand.
To determine the current status in various aspects of gastric cancer in
Thai patients, we retrospectively reviewed the records of 119 patients
with histologically proven gastric cancer in King Chulalongkorn Memorial
Hospital during the five-year period from 1994 to 1998. There were 72
males (60.5%) and 47 females (39.5%) with ages ranging from 22 to 91
years (mean age 60.2+/-15.1 years). Among these, 20 patients (16.8%)
were younger than 40 years. The duration of symptoms prior to first
presentation averaged 20 weeks and dyspepsia and weight loss were the
most common complaints. Lesion location was lower third in 40.3 per
cent, middle third in 31.9 per cent, upper third in 15.1 per cent and
entire stomach in 3.4 per cent of patients. Adenocarcinoma was the most
common histological finding (91.6%), followed by lymphoma and
leiomyosarcoma (3.4% each). Helicobacter pylori infection was detected
in 17 of 25 (68%). The TMN staging was as follows: stage II, 5.9 per
cent; stage III, 9.2 per cent; and stage IV, 68.9 per cent. (the stage
was unknown in 16%). The overall 1-year, 2-year and 5-year survival
rates were 51.6 per cent, 17.5 per cent and 4.4 per cent, respectively.
Management was surgical treatment in 58.9 per cent (total gastrectomy
14.5%, subtotal gastrectomy 33.3% and palliative bypass surgery in
11.1%). Systemic chemotherapy was the primary modality of therapy in
16.8 per cent and was adjuvant therapy in 18.5 per cent. The median
survival time of resectable cases was 1.00+/-0.53 years, significantly
longer than that of unresectable cases (0.11+/-0.03 years) (p=0.0025).
However, the administration of chemotherapy did not improve the survival
rate. It is concluded that, in Thailand, gastric cancer continues to be
an important health problem and is generally associated with a poor
prognosis.
7
UI - 21356437
AU - Caruso DA; McIntyre BW
TI -
In an adhesion dependent human gastric adenocarcinoma cell line,
integrin ligation without adhesion rescues from anoikis but is not
sufficient for cell cycle progression.
SO - Cell Death Differ 2001 Jul;8(7):665-78
AD - Department of Immunology, University of Texas MD Anderson Cancer Center,
1515 Holcombe Blvd., Houston, TX 77030, USA.
STAD cells are the adherent parental apoptotic line from which two
sublines were cloned that differed in their response to suspended
culturing conditions, one clone STAD.APO is apoptotic and the other
STAD.ARR goes into cell cycle arrest. Using this system we have found
that the addition of soluble collagen can rescue STAD and STAD.APO cells
from anoikis, and it can also affect STAD.ARR cells by overcoming the
suspension induced cell cycle arrest. In contrast, when cells were
cultured with a soluble anti-beta1 integrin mAb 33B6, the apoptotic
clones again were rescued from anoikis, but the cell cycle arresting
clone remained quiescent. This result was somewhat surprising as it is
generally accepted that cytoskeletal rearrangements that accompany
integrin mediated adhesion and cell shape changes are required for the
abrogation of anoikis, and it was unexpected that differences in the
mechanism used for integrin triggering would yield variable results on
growth regulation. This observation led us to further examine whether
the addition of a monovalent anti-beta1 integrin agent could produce
similar results as intact mAb. Therefore we employed Fab fragments of
33B6 in our culturing assay and found that indeed monovalent binding was
capable of saving STAD and STAD.APO cells from anoikis but did not have
an effect on STAD.ARR cells. Therefore in this study we have observed
that integrin mediated dependent survival can occur by mere ligation of
the beta1 integrin subunit, but that cell cycle arrest due to suspended
conditions can not. Thus integrins can play differential roles in cell
fate decisions and mediate these effects by different mechanisms.
8
UI - 21367952
AU - Kong G; Oga A; Park CK; Kawauchi S; Furuya T; Sasaki K
TI -
DNA sequence copy number aberrations associated with histological
subtypes and DNA ploidy in gastric carcinoma.
SO - Jpn J Cancer Res 2001 Jul;92(7):740-7
AD - Department of Pathology, College of Medicine, Hanyang University, Seoul,
133-791, Korea. kohsuke@po.cc.yamaguchi-u.ac.jp
We have analyzed DNA sequence copy number aberrations (DSCNAs) and DNA
ploidy by using comparative genomic hybridization and laser scanning
cytometer in gastric carcinomas (GCs) to elucidate the genomic
aberrations in relation to clinicopathological parameters. Thirty-two
out of 33 cases showed one or more DSCNAs with a mean number of 11.7 per
tumor. High-level gains were detected at 2p, 3q, 6p, 7p, 7q, 8q, 12p,
13q, 19q, and 20q. Frequency of gross genomic abnormalities and
chromosome regions that have genomic aberrations were similar in both
intestinal- and diffuse-type GCs, except aberrations at 8p, 9p, 12q, and
20q. The overall number of DSCNAs was significantly greater in DNA
aneuploid tumors than that in DNA diploid tumors. We detected genomic
aberrations characterized by histological subtype, tumor location, and
DNA ploidy status: gain of 20q and losses of 8p and 9p in
intestinal-type GCs, gains of 8p and 12q in diffuse-type GCs, gain of
20q in the lower third GCs, and loss of 5q, 9p, 10q, 16q, and 18q in DNA
aneuploid GCs. Furthermore, 5q loss is associated with DNA aneuploidy (P
= 0.0001) or the total number of losses (P = 0.001), gain + losses (P =
0.004), and high-level gains (P = 0.001) in GCs. Among these loci,
chromosome 8p was unique. Gain of 8p was more common in diffuse-type GC,
whereas loss of 8p was more frequently detected in intestinal-type GC.
In conclusion, we describe chromosomal regions of 5q, 8p, and 20q, which
are of interest for further investigation of GCs.
9
UI - 21367962
AU - Matsuo A; Watanabe A; Takahashi T; Futamura M; Mori S; Sugiyama Y;
TI -
Takahashi Y; Saji S
A simple method for classification of cell death by use of thin layer
collagen gel for the detection of apoptosis and/or necrosis after cancer
chemotherapy.
SO - Jpn J Cancer Res 2001 Jul;92(7):813-9
AD - Second Department of Surgery, Gifu University School of Medicine, Gifu
500-8705, Japan. atsushim@cc.gifu-u.ac.jp
To assess the efficacy of cancer chemotherapy, an important index is
apoptosis of the target cells, which can usually be confirmed by
electron microscopy (EM). We established a new experimental technique,
whereby cancer cells (MKN45) were distributed in thin collagen gel as
one or two cell layers, and cultured with anti-cancer drugs (5-FU and
CDDP). The cells were stained with fluorescent Hoechst 33258 (Ho) and
photographed, then with hematoxylin and eosin (H&E) and again
photographed, and processed for EM. This approach allowed us to
characterize the patterns of death of single cells in detail. There were
six patterns of cell damage: two patterns of apoptosis, early peripheral
condensation of chromatin and late apoptotic bodies, two patterns of
necrosis, cytoplasmic swelling and washed-out images, and two further
patterns, with morphological features of both apoptosis and necrosis,
neither classified into necrosis nor apoptosis. The results show that
cell death patterns can be mostly determined by combining observations
of Ho and H&E-stained cells without the necessity for EM observation.
10
UI - 21385137
AU - Matsutani N; Yokozaki H; Tahara E; Tahara H; Kuniyasu H; Haruma K;
TI -
Chayama K; Yasui W; Tahara E
Expression of telomeric repeat binding factor 1 and 2 and
TRF1-interacting nuclear protein 2 in human gastric carcinomas.
SO - Int J Oncol 2001 Sep;19(3):507-12
AD - First Department of Pathology, Hiroshima University School of Medicine,
Hiroshima 734-8511, Japan.
Telomeric repeat binding factor 1 (TRF1) and 2 (TRF2) may play key roles
in the maintenance of telomere function. TRF1 negatively regulates
telomere elongation, while TRF2 protects the chromosome ends by
inhibiting end-to-end fusions. We examined the expression of TRF1 and
TRF2 in 20 gastric carcinomas by reverse transcription polymerase chain
reaction and then analyzed the relation with telomerase activity and
other telomerase components such as human telomerase reverse
transcriptase (TERT), human telomerase RNA component (hTR), human
telomerase-associated protein (TEP1) and TRF1-interacting,
ankyrin-related ADP-ribose polymerase (tankyrase) as well as
TRF1-interacting nuclear protein 2 (TIN2). Of 20 gastric carcinomas
examined, 10 (50%) and 12 (60%) expressed TRF1 and TRF2 at higher levels
than did non-neoplastic mucosa, respectively. No obvious correlation was
observed between TRF1 expression and telomerase activity or expression
of TERT, hTR and TEP1. Carcinomas with high TRF1 expression expressed
significantly higher levels of tankyrase and TIN2 than did those with
low TRF2 expression (p<0.05). The telomerase activities and the levels
of TERT, hTR and TEP1 showed tendency to be lower in tumors expressing
TRF1 at low levels, although it was not significant. On the other hand,
carcinomas with short telomere length (shorter than 2 Kbp) expressed
significantly stronger telomerase activities and higher TRF1 expression
(p<0.05) and tended to express TRF2 and TIN2 at higher levels than those
with long telomere length. The results suggest that gastric carcinomas
with short telomeres need high levels of telomerase activity and large
quantity of TRFs and TIN2, whereas those with long telomeres do not
require high levels of telomerase activity and telomere associated
proteins.
11
UI - 21385141
AU - Kirikoshi H; Sekihara H; Katoh M
TI -
Up-regulation of WNT10A by tumor necrosis factor alpha and Helicobacter
pylori in gastric cancer.
SO - Int J Oncol 2001 Sep;19(3):533-6
AD - Genetics and Cell Biology Section, Genetics Division, National Cancer
Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Japan.
WNT signaling pathway is implicated in carcinogenesis and embryogenesis.
We have previously cloned and characterized WNT10A and WNT6, which are
clustered in human chromosome 2q35 region. In this study, we
investigated expression of WNT10A and WNT6 in gastric cancer. The 3.0-
and 2.4-kb WNT10A mRNAs were expressed in gastric cancer cell lines
MKN7, MKN45 and MKN74. The 2.0-kb WNT6 mRNA was expressed in gastric
cancer cell lines MKN28 and MKN74. WNT10A was up-regulated in 3 out of 6
cases of primary gastric cancer, while WNT6 was not up-regulated in
primary gastric cancer. Effects of inflammatory cytokines and
Helicobacter pylori (H. pylori) on expression of WNT10A and WNT6 were
next investigated. Interferon gamma (IFNgamma) failed to induce
up-regulation of WNT10A and WNT6. Tumor necrosis factor alpha (TNFalpha)
induced up-regulation of WNT10A in MKN45 cells. Up-regulation of WNT10A
reached maximum at 6 h after TNFalpha treatment. H. pylori also induced
up-regulation of WNT10A in MKN45 cells. These results strongly suggest
that up-regulation of WNT10A induced by TNFalpha and H. pylori might
play key roles in human gastric cancer through activation of
WNT--beta-catenin--TCF signaling pathway.
12
UI - 21430303
AU - Moshkovitz M; Niv Y
TI -
[Helicobacter pylori and gastric cancer]
SO - Harefuah 2001 Aug;140(8):738-43
13
UI - 21445653
AU - Vogel I; Kalthoff H
TI -
Disseminated tumour cells. Their detection and significance for
prognosis of gastrointestinal and pancreatic carcinomas.
SO - Virchows Arch 2001 Aug;439(2):109-17
AD - Department of General and Thoracic Surgery, University of Kiel, Germany.
ivogel@surgery.uni-kiel.de
Metastatic spread is a major factor in the prognosis of cancer patients.
Early detection and eradication of circulating tumour cells prior to the
development of metastases could help to improve the outcome of patients
after tumour resection. Disseminated tumour cells have been detected in
different compartments of the body using cytological and immunostaining
methods and, more recently, using different molecular biological
techniques. The most frequently studied body compartments are the bone
marrow, peritoneal cavity, blood and lymph nodes, but other body fluids
such as urine, bile, pancreatic juice and sputum have also been
analysed. At all of these sites, tumour cells have been detected.
However, the specificity and sensitivity of the methods and their
prognostic impact are still being debated. This review discusses the
accuracy of the detection methods and the prognostic value of detecting
disseminated tumour cells in the bone marrow, blood and peritoneal
lavage of patients with colorectal, gastric and pancreatic carcinomas.
14
UI - 21445659
AU - Chiaravalli AM; Cornaggia M; Furlan D; Capella C; Fiocca R; Tagliabue G;
TI -
Klersy C; Solcia E
The role of histological investigation in prognostic evaluation of
advanced gastric cancer. Analysis of histological structure and
molecular changes compared with invasive pattern and stage.
SO - Virchows Arch 2001 Aug;439(2):158-69
AD - Department of Pathology, University of Insubria, Varese, Italy.
The relative contribution of tumour histology or molecular changes,
compared with invasion pattern or stage, to prognostic assessment of
gastric cancer was investigated in a series of 185 advanced (T2 to T4,
stage IB to IV) cancers that had undergone intentionally curative
surgery at Varese General Hospital. Survival analysis of the
histological types considered in commonly used classifications, such as
Lauren, Kubo, the World Health Organization (WHO) and related
classifications, allowed separation of a small high-grade (Hg, 12 cases)
group of adenosquamous, anaplastic and small cell endocrine carcinomas
from a large cohesive group (C, 86 glandular or solid cancers) and from
another large (87 cases) group of tumours with dissociated cells [29
diffuse (D) and 58 mixed (M) tumours]. Univariate and multivariate
analysis showed the independent prognostic value of this C/M+D/Hg
classification approach, which proved superior to other classifications
and to cell dissociation at the growing front or angio, lympho and
neuro-invasion. Expression of sialyl Lewis(c), the DUPAN-2 antigen,
proved to be an independent predictor of worse survival among tumours
beyond stage I, showing an exclusively or predominantly cohesive
structure. Microsatellite instability (MSI) predicted favourable
survival in purely cohesive tumours of intermediate (II) stage,
especially of solid/medullary and lymphoid
stroma/lympho-epithelioma-like structure, among which two distinct
tumour subsets were characterised, one MSI-positive and the other
Epstein-Barr virus positive. T2NOM0 (stage IB) tumours showed mostly
favourable survival independently from histological type, invasive
pattern, DUPAN-2 or MSI status. It is concluded that an appropriate
histological evaluation, coupled with sialylated glycoproteins
histochemistry and, for stage-II tumours, MSI tests may contribute
significantly to prognostic assessment of tumours beyond stage I.
However, the stage itself, with special reference to lymph-node
metastases and invasion level beyond subserosa, remains the most
important prognostic clue for gastric cancer.
15
UI - 21423019
AU - Mashino K; Sadanaga N; Tanaka F; Yamaguchi H; Nagashima H; Inoue H;
TI -
Sugimachi K; Mori M
Expression of multiple cancer-testis antigen genes in gastrointestinal
and breast carcinomas.
SO - Br J Cancer 2001 Sep 1;85(5):713-20
AD - Department of Surgery, Medical Institute of Bioregulation, Kyushu
University, 4546 Tsurumibaru, Beppu, Japan.
Cancer-testis antigens (CTAs) such as MAGE are selectively expressed in
various types of human neoplasms but not in normal tissues other than
testis. This characteristic feature of CTAs makes them promising
antigens for cancer-specific immunotherapy. A critical requirement for
this therapy is identification of promising antigens. In this study, we
investigated the expression of 6 genes recently identified by
serological analysis of antigens by recombinant expression (SEREX)
libraries: NY-ESO-1, LAGE-1, SCP-1, SSX-1, SSX-2, and SSX-4, in many
surgical samples of gastrointestinal and breast carcinomas using reverse
transcription-polymerase chain reaction. We found relatively high
expression of SCP-1 (23.5%) and SSX-4 (20.6%) in gastric carcinoma,
LAGE-1 (39.1%) and NY-ESO-1 (23.9%) in oesophageal carcinoma, and SCP-1
(34.1%) in breast carcinoma. We also found frequent synchronous
expression with MAGE, including LAGE-1 (46.2%) in oesophageal carcinoma,
SSX-4 (46.7%) in gastric carcinoma, and SCP-1 (38.3%) in breast
carcinoma. Immunohistochemical analysis of the tumour samples expressing
both MAGE-4 and NY-ESO-1 genes demonstrated differences in distribution
between MAGE-4 and NY-ESO-1 in serial sections. We concluded that
NY-ESO-1, LAGE-1, SCP-1 and SSX-4 genes may be promising candidates for
cancer-specific immunotherapy in addition to MAGE, and that polyvalent
cancer vaccines may be useful in cases of heterogeneous expressions of
CTA genes in gastrointestinal and breast carcinomas. Copyright 2001
Cancer Research Campaign.
16
UI - 21423029
AU - Sobin LH
TI -
TNM classification: clarification of number of regional lymph nodes for
pN0.
SO - Br J Cancer 2001 Sep 1;85(5):780
17
UI - 21022874
AU - De Stefani E; Boffetta P; Ronco AL; Brennan P; Deneo-Pellegrini H;
TI -
Carzoglio JC; Mendilaharsu M
Plant sterols and risk of stomach cancer: a case-control study in
Uruguay.
SO - Nutr Cancer 2000;37(2):140-4
AD - Registro Nacional de Cancer, Montevideo, Uruguay.
In 1997-1999, 120 incident and histologically verified cases of stomach
cancer were frequency matched on age, gender, residence, and urban/rural
status with 360 controls to study the role of diet in gastric cancer in
Uruguay. We focused on the role of plant sterols (beta-sitosterol,
campesterol, stigmasterol, and total plant sterols) after controlling
for major confounders. Total phytosterols were associated with a strong
inverse relationship with stomach cancer (odds ratio of stomach cancer
for total phytosterol intake in the highest tertile = 0.33, 95%
confidence interval = 0.17-0.65). Joint exposure to high intake of total
phytosterol and alpha-carotene was also inversely associated with
gastric cancer risk (odds ratio = 0.09, 95% confidence interval =
0.02-0.32). High intake of total plant sterols explained most of the
attenuation in risk of gastric cancer associated with vegetable and
fruit intakes.
18
UI - 21262956
AU - Caporale A; Cosenza UM; Vestri AR; Giuliani A; Costi U; Galati G;
TI -
Cannaviello C; Franchi F
Has desmoplastic response extent protective action against tumor
aggressiveness in gastric carcinoma?
SO - J Exp Clin Cancer Res 2001 Mar;20(1):21-4
AD - Dept. of Surgery Pietro Valdoni, Universita di Roma La Sapienza, Rome,
Italy.
A clinical assessment of protective action of desmoplastic response by
limiting tumor aggressiveness has been carried out in 171 patients with
gastric carcinoma, surgically treated at the First Surgical Clinic of
the University of Rome "La Sapienza" between 1988-1999. A univariate
statistical analysis was performed using Kaplan-Meier method for:
desmoplastic reaction, age, sex, histologic type, tumor size, stage,
lymphonodal status and metastases. To determine the influence of these
factors on prognosis, the Cox regression was applied. We found a
significant association between desmoplastic reaction extent and
presence or absence of metastases (p= 0.026), lymphonodal involvement (p
= 0.05), stage (p = 0.036). In the univariate analysis, survival was
significantly related to sex (p = 0.012), tumor size (p = 0.009),
lymphonodal involvement (p = 0.000), metastases (p = 0.000), stage (p =
0.000), desmoplastic reaction extent (p = 0.05); age and histologic type
showed no relationship (p = n.s.). The desmoplastic response extent is
not a protective factor against tumor invasiveness in gastric carcinoma,
on the contrary it may be considered a negative prognostic factor.
19
UI - 21271458
AU - Fujii K; Fujioka S; Kato K; Machiki Y; Kutsuna Y; Ishikawa A; Takamizawa
TI -
J; Ko K; Yoshida K; Nimura Y
Resection of liver metastasis from gastric adenocarcinoma.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):368-71
AD - Department of Surgery, Kiryu Kousei General Hospital, Kiryu, Japan.
BACKGROUND/AIMS: To determine the factors influencing the prognosis of
patients undergoing resection of liver metastases from gastric
adenocarcinoma. METHODOLOGY: Over a 10-year period, at Kiryu Kousei
General Hospital, 12 patients underwent potentially curative hepatectomy
for metastatic adenocarcinoma of gastric origin. Two patients were
excluded from this study, one because of postoperative death and one due
to insufficient follow-up. We retrospectively examined the following
factors: including TNM classification of the primary tumor, disease-free
interval between gastric and hepatic resection, number and maximum
diameter of the metastases, histological differentiation of the
metastases, and the presence of lymphocyte aggregation enclosing the
metastatic lesions. Survival rates were estimated by the Kaplan-Meier
method and the weighting of each factor was compared by the log-rank
test. RESULTS: The overall 5-year survival rate of the 10 patients was
10%. The median survival time after hepatectomy was 16.3 months, ranging
from 3.1 to 245.7 months. Eight patients died of recurrent cancer and 1
died of unrelated septic shock with no evidence of cancer recurrence.
Only one patient was alive without recurrence at the time of maximum
follow-up. A significant survival advantage was noted in patients with
disease-free interval > or = 1 year, and those with metastatic tumors <
5 cm in maximum diameter and/or enclosed by the aggregated lymphocytes,
when compared with patients with disease-free interval < 1 year and
those with metastatic tumors > or = 5 cm and/or directly infiltrated
hepatic parenchyma. CONCLUSIONS: It was suggested that hepatectomy
should be attempted in patients where the disease-free interval was > or
= 1 year and with metastatic nodules < 5 cm. Lymphocyte aggregation
around the metastatic tumor is a good prognostic sign for long-term
survival.
20
UI - 21271483
AU - Saito S; Kasai Y; Nomoto S; Fujiwara M; Akiyama S; Ito K; Nakao A
TI -
Polymorphism of tumor necrosis factor in esophageal, gastric or
colorectal carcinoma.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):468-70
AD - Department of Surgery II, School of Medicine, Nagoya University, 65
Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan.
BACKGROUND/AIMS: Several microsatellite polymorphisms located in the
tumor necrosis factor locus on the chromosomal region 6p21.3 in the
major histocompatibility complex region have been associated with
malignant neoplasms and autoimmune diseases. In this study, we focused
on the polymorphisms of tumor necrosis factor a and d from
gastrointestinal carcinoma patients to ascertain whether they can be
useful to predict these neoplasms. METHODOLOGY: We examined esophageal,
gastric, and colorectal cancers (47, 53, 77 patients, respectively), and
213 normal controls. To compare the microsatellite polymorphisms of
tumor necrosis factor a, d in Japanese individuals, dioxyribonucleic
acids were extracted from normal mucosa (cancer patients) and from
peripheral blood monocytes (the normal controls) by polymerase chain
reaction. RESULTS: The frequency of tumor necrosis factor a3 allele was
significantly higher in gastric cancer (P = 0.012) and that of tumor
necrosis factor d7 allele was significantly higher in the colorectal
cancer than the normal controls (P = 0.037). That of tumor necrosis
factor a10 was significantly lower in the gastric cancer than the normal
controls (P = 0.008). CONCLUSIONS: Microsatellite polymorphisms of tumor
necrosis factor a and d might be significantly correlated with
carcinogenesis of specific neoplasms, and may be useful for predicting
these cancers.
21
UI - 21381299
AU - Genta RM; Rugge M
TI -
Review article: pre-neoplastic states of the gastric mucosa--a practical
approach for the perplexed clinician.
SO - Aliment Pharmacol Ther 2001 Jun;15 Suppl 1():43-50
AD - Baylor College of Medicine, VAMC-2002 Holcombe Blvd., Houston, TX 77030,
USA. rmgenta@bcm.tmc.edu
The sequence leading to gastric cancer can be schematically reduced to
Helicobacter pylori infection-chronic gastritis-atrophy-intestinal
metaplasia-dysplasia-neoplasia. Although clinicians have not yet
developed a uniform approach to the treatment of gastritis (when should
H. pylori infection be treated?), the entity itself is not the subject
of controversy. All other lesions are still the focus of debate. There
are no guidelines for the management of patients with intestinal
metaplasia; pathologists are still searching for universal diagnostic
criteria for atrophic gastritis; dysplasia and early neoplasia have
elicited scientific diatribes between Japanese and Western pathologists.
Amidst such controversies and in the absence of guidelines to regulate
the management of gastric lesions, the responsibility to provide
sensible clinical advice is often bestowed upon pathologists. This
review discusses whether pathologists have access to sufficient evidence
to provide the requested advice, and whether a consensus on the
management of gastric "pre-neoplastic" states is within reach. We
conclude that, although many sensible and useful definitions, criteria
and classifications are being generated, the final decision on how to
manage the individual patient with gastric lesions will continue to be
based on the communication between pathologist and clinician.
22
UI - 21369700
AU - Stocks SC; Pratt N; Sales M; Johnston DA; Thompson AM; Carey FA;
TI -
Kernohan NM
Chromosomal imbalances in gastric and esophageal adenocarcinoma:
specific comparative genomic hybridization-detected abnormalities
segregate with junctional adenocarcinomas.
SO - Genes Chromosomes Cancer 2001 Sep;32(1):50-8
AD - Department of Molecular and Cellular Pathology, University of Dundee,
Tayside University Hospitals Trust, Dundee, United Kingdom.
The incidence of adenocarcinoma arising at the esophagogastric junction
(EGJ) is increasing at a rate greater than that for any other form of
solid malignancy. Commensurate with this, the incidence of
histologically similar tumors arising in the gastric body and antral
mucosa is declining. The increased incidence of the proximal group of
tumors may reflect, in part, the higher prevalence of Barrett esophagus.
These epidemiological features suggest that histologically similar
tumors arising at the EGJ and from the distal stomach are different,
which may be reflected in the genetic abnormalities that characterize
the two groups of tumors. The purpose of this study was to screen
genomic DNA from adenocarcinomas of the esophagus and stomach for
regions of chromosomal imbalance, using comparative genomic
hybridization to determine whether tumors at the EGJ (junctional tumors)
have a different profile compared with tumors of the distal stomach.
Tumor samples were derived from a series of 48 gastroesophageal
adenocarcinomas (20 junctional and 28 distal) that were acquired
prospectively from patients undergoing esophagogastrectomy. These tumors
are characterized by several regions of chromosomal imbalance with no
obvious correlation between most regions of abnormal copy number and
tumor type. However, our study shows for the first time cytogenetic
abnormalities (5p+ and 18q-) that identify statistically significant
differences (P < 0.02 and < 0.05, respectively) between junctional and
distal gastric tumors. These differences are gain of 5p (55% [11/20] of
junctional tumors vs. 21% [6/28] of distal gastric tumors) and loss of
18q (25% [5/20] cases of junctional tumors vs. 4% [1/28] of distal
tumors) segregating with tumors of the EGJ. These abnormalities may
distinguish distinct tumor subtypes that are recognized in
epidemiological and clinical studies but that are otherwise
histologically identical. Copyright 2001 Wiley-Liss, Inc.
23
UI - 21369702
AU - Zheng YL; Herr AM; Jacobson BA; Ferrin LJ
TI -
High-density allelotype of the commonly studied gastric cancer cell
lines.
SO - Genes Chromosomes Cancer 2001 Sep;32(1):67-81
AD - National Cancer Institute, National Institutes of Health, Bethesda,
Maryland, USA.
Gastric cancer is one of the leading causes of death from cancer
throughout the world, and studies to elucidate the genetic defects found
in this type of cancer are growing in number. Increasingly sophisticated
techniques and the sequencing of the human genome have had an impact on
the scope of such studies. While the use of tumor specimens remains
popular, more emphasis is being placed on cell lines as model systems
where specific data can be directly combined with results from other
studies. This article describes a genetic survey of the most widely used
gastric adenocarcinoma cell lines. The allelotype at 351 polymorphic
loci in 14 cell lines was obtained, and the results from the 4,900
polymerase chain reactions are displayed. In addition to confirming loss
of heterozygosity on chromosome arms 6p, 7q, 17p, and 18, additional
deletions on arm 5p and the pericentromeric regions of chromosomes 1 and
10 were detected. Areas that might contain homozygous deletions or
amplifications also were mapped. The rate of microsatellite instability
was quantified and shown to vary greatly among the different cell lines.
Most important, this study serves as a genetic scaffold for the
integration of past and future studies on the nature of the genetic
defects in gastric cancer. Copyright 2001 Wiley-Liss, Inc.
24
UI - 21424853
AU - Waller MB
TI -
Evaluation and management of gastric adenocarcinoma.
SO - Nurs Clin North Am 2001 Sep;36(3):543-52, xi
AD - Department of Surgery, The University of Texas MD Anderson Cancer
Center, Houston, Texas 77030, USA. mbrame@mdanderson.org
This article reviews the epidemiology, cause, and current staging of
gastric adenocarcinoma. An in-depth discussion regarding patient
assessment and treatment options is presented. Advanced disease
management and clinical trials are reviewed.
25
UI - 20307241
AU - Laine L; Ahnen D; McClain C; Solcia E; Walsh JH
TI -
Review article: potential gastrointestinal effects of long-term acid
suppression with proton pump inhibitors.
SO - Aliment Pharmacol Ther 2000 Jun;14(6):651-68
AD - University of Southern California School of Medicine, Los Angeles,
California 90033, USA. llaine@usc.edu
This review examines the evidence for the development of adverse effects
due to prolonged gastric acid suppression with proton pump inhibitors.
Potential areas of concern regarding long-term proton pump inhibitor use
have included: carcinoid formation; development of gastric
adenocarcinoma (especially in patients with Helicobacter pylori
infection); bacterial overgrowth; enteric infections; and malabsorption
of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may
lead to enterochromaffin-like cell hyperplasia, but has not been
demonstrated to increase the risk of carcinoid formation. Long-term
proton pump inhibitor treatment has not been documented to hasten the
development or the progression of atrophic gastritis to intestinal
metaplasia and gastric cancer, although long-term studies are required
to allow definitive conclusions. At present, we do not recommend that
patients be tested routinely for H. pylori infection when using proton
pump inhibitors for prolonged periods. Gastric bacterial overgrowth does
increase with acid suppression, but important clinical sequelae, such a
higher rate of gastric adenocarcinoma, have not been seen. The risk of
enteric infection may increase with acid suppression, although this does
not seem to be a common clinical problem with prolonged proton pump
inhibitor use. The absorption of fats and minerals does not appear to be
significantly impaired with chronic acid suppression. However, vitamin
B12 concentration may be decreased when gastric acid is markedly
suppressed for prolonged periods (e.g. Zolllinger-Ellison syndrome), and
vitamin B12 levels should probably be assessed in patients taking
high-dose proton pump inhibitors for many years. Thus, current evidence
suggests that prolonged gastric acid suppression with proton pump
inhibitors rarely, if ever, produces adverse events. Nevertheless,
continued follow-up of patients taking proton pump inhibitors for
extended periods will provide greater experience regarding the potential
gastrointestinal adverse effects of long-term acid suppression.
26
UI - 21282751
AU - Song SH; Jong HS; Choi HH; Inoue H; Tanabe T; Kim NK; Bang YJ
TI -
Transcriptional silencing of Cyclooxygenase-2 by hyper-methylation of
the 5' CpG island in human gastric carcinoma cells.
SO - Cancer Res 2001 Jun 1;61(11):4628-35
AD - Cancer Research Institute, Seoul National University College of
Medicine, Seoul 110-799, Korea.
It has been well established that overexpression of Cyclooxygenase-2
(Cox-2) in epithelial cells inhibits apoptosis and increases the
invasiveness of malignant cells, favoring tumorigenesis and metastasis.
However, the molecular mechanism that regulates Cox-2 expression has not
been well defined in gastric carcinoma. In this study, we examined
whether the Cox-2 expression could be regulated by hyper-methylation of
the Cox-2 CpG island (spanning from -590 to +186 with respect to the
transcription initiation site) in human gastric carcinoma cell lines. By
Southern analysis, we found that three gastric cells (SNU-601, -620, and
-719) without Cox-2 expression demonstrated hyper-methylation at the
Cox-2 CpG island. A detailed methylation pattern using bisulfite
sequencing analysis revealed that all of the CpG sites were completely
methylated in SNU-601. Treatment with demethylating agents effectively
reactivated the expression of Cox-2 and restored IL-1beta sensitivity in
the previously resistant SNU-601. By transient transfection experiments,
we demonstrate that constitutively active Cox-2 promoter activities were
exhibited even without an exogenous stimulation in SNU-601. Furthermore,
when the motif of the nuclear factor for interleukin-6 expression site,
the cyclic AMP response element, or both was subjected to point
mutation, the constitutive luciferase activity was markedly reduced. In
addition, Cox-2 promoter activity was completely blocked by in vitro
methylation of all of the CpG sites in the Cox-2 promoter region with
SssI (CpG) methylase in SNU-601. Taken together, these results indicate
that transcriptional repression of Cox-2 is caused by hyper-methylation
of the Cox-2 CpG island in gastric carcinoma cell lines.
27
UI - 21330627
AU - Hirai T; Toge T
TI -
[Treatment of lymph node metastasis from the viewpoint of surgical
oncology]
SO - Nippon Geka Gakkai Zasshi 2001 Jun;102(6):453-8
AD - Department of Surgical Oncology, Research Institute for Radiation
Biology and Medicine, Hiroshima University, Hiroshima, Japan.
We have investigated methods to predict lymph node metastasis in early
gastric cancer. First, the efficacy of fluorescence in situ
hybridization (FISH) using the dual-color method was evaluated as a
potential marker of lymph node metastasis in 20 early gastric cancers. A
significant increase in the fraction of cells with a decrease in p53 was
observed in early gastric cancer compared with normal tissues. More
importantly, a significant increase in the fraction of cells with p53
deletion was observed in patients with lymph node metastasis. The
predictive accuracy was 45%. Second, the relationship between the degree
of expression of biological markers and lymph node metastasis was
examined. High expression of p27 and cyclin E had a strong correlation
with lymph node metastasis. Moreover, all patients with combined high
expression of p27, cyclin E, and matrix metalloproteinase-9 had lymph
node metastasis. However, these represented only 21% of cases with lymph
node metastasis. Difficulty in the clinical use of these biological
markers to detect lymph node metastasis depends on the feedback
mechanism of cell cycle regulators or heterogeneity of the lesion. These
problems should be resolved in the near feature.
28
UI - 21366204
AU - Nojiri T; Ikegami M
TI -
Multiple minute carcinoids in type A gastritis: attempt at 3-D
reconstruction.
SO - Pathol Int 2001 Jul;51(7):504-10
AD - Department of Pathology, Jikei Universit
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