Digitum Colección:http://hdl.handle.net/10201/946082024-03-28T17:38:50Z2024-03-28T17:38:50ZImpact of tumor angiogenic profile on the
outcome of patients with metastatic breast
carcinoma treated with weekly docetaxel. A
Hellenic Cooperative Oncology Group (HeCOG) studyKourea, Helen P.Kotoula, VassilikiKoutras, AngelosAlexopoulou, ZoiPapaspirou, IreneSkarlos, Dimosthenis V.Efstratiou, IoannisBobos, MattheosZagouri, FloraPapakostas, PavlosPectasides, DimitriosChrisafi, SofiaVarthalitis, IoannisAravantinos, GerasimosKosmidis, ParisBafaloukos, DimitriosScopa, Chrisoula D.Fountzilas, Georgehttp://hdl.handle.net/10201/964662020-09-24T23:18:17Z2015-01-01T00:00:00ZTítulo: Impact of tumor angiogenic profile on the
outcome of patients with metastatic breast
carcinoma treated with weekly docetaxel. A
Hellenic Cooperative Oncology Group (HeCOG) study
Autor/es principal/es: Kourea, Helen P.; Kotoula, Vassiliki; Koutras, Angelos; Alexopoulou, Zoi; Papaspirou, Irene; Skarlos, Dimosthenis V.; Efstratiou, Ioannis; Bobos, Mattheos; Zagouri, Flora; Papakostas, Pavlos; Pectasides, Dimitrios; Chrisafi, Sofia; Varthalitis, Ioannis; Aravantinos, Gerasimos; Kosmidis, Paris; Bafaloukos, Dimitrios; Scopa, Chrisoula D.; Fountzilas, George
Resumen: Background: Metronomic taxane
administration has putative antiangiogenic properties.
Herein, we examined the baseline tumor angiogenic
profile of patients with metastatic breast carcinoma
(MBC) in a prospective-retrospective translational
research study. The interplay between the angiogenic
factors expressed in the tumors and their prognostic
value in MBC were investigated.
Patients and Methods: Tumor tissues from patients
with MBC treated with weekly docetaxel (n=159) were
examined by immunohistochemistry for VEGF-A,
VEGF-C, VEGFR-1, VEGFR-2, VEGFR-3 and
osteopontin (OPN) and by mRNA analysis for
expression of VEGF-A, VEGFxxxa, VEGFxxxb, VEGFC, thrombospondin-1 (THBS-1), hypoxia-inducible
factor-1α (HIF-1α) and von Hippel-Lindau (VHL) genes. Associations between these parameters and
outcome were statistically analyzed.
Results: Statistically significant correlations were
identified between almost all biomarkers examined in
continuous form, particularly at the mRNA level: VEGFA with VEGFxxxa (rho=0.70); VEGF-C with
VEGFxxxa, VEGFxxxb and VHL (rho=0.51, 0.60 and
0.44 respectively); HIF-1α with VEGF-C and THBS1
(rho=0.48 and 0.45). High VEGF-A mRNA was
associated with worse survival (p=0.0279) and
marginally with progression free survival (PFS).
Intratumoral co-expression of VEGFR-1 and VEGFR-2
proteins was associated with more favorable survival
(p=0.0337). In multivariate analysis, only high VEGF-A
mRNA levels retained their prognostic role for worse
PFS and survival (PFS: HR=2.34, 95% CI=1.25-4.40,
p=0.0080; survival: HR=3.15, 95% CI=1.48-6.72,
p=0.0029).
Conclusions: In MBC, this study confirms the
adverse prognostic effect of high intratumoral VEGF-A
mRNA and reveals the combined VEGFR-1/VEGFR-2 protein expression as a potentially favorable
prognosticator, which merits further evaluation in larger
studies.2015-01-01T00:00:00ZDiameter of involved nerves is a valuable
prognostic factor for gastric cancerZhou, Zhi-huaZhang, Jian-dongZhao, Hai-BinWu, Yao-yihttp://hdl.handle.net/10201/964652020-09-24T23:14:53Z2015-01-01T00:00:00ZTítulo: Diameter of involved nerves is a valuable
prognostic factor for gastric cancer
Autor/es principal/es: Zhou, Zhi-hua; Zhang, Jian-dong; Zhao, Hai-Bin; Wu, Yao-yi
Resumen: The prognostic role of perineural invasion
(PNI) in gastric cancer remains unclear. We
hypothesized that the diameter of the tumor-involved
nerves might be a useful indicator for prognosis. By
labeling nerves and cancer cells in 204 cases of gastric
cancer with single or double immunochemistry, we
found that 146 cases were PNI positive and that 58 were
PNI negative. For each case with PNI, the maximum
diameter of the involved nerve was measured
microscopically. Then, we correlated this parameter with
the patients’ 5-year overall survival, and receiver
operating curves were used to determine the cutoff
value. We found that the optimal cutoff value for
predicting 5-year survival was 65 µm (sensitivity 76.9%,
specificity 70.0%). Next, all 204 patients were classified
into two groups as follows: Group A, PNI-positive cases
in which the largest involved nerves were ≥65 µm in
diameter (110 cases); Group B, PNI-positive cases in
which the largest involved nerves were <65 µm and all
PNI-negative cases (94 cases). Compared with Group A,
Group B had a better 5-year survival (74.5% vs 27.3%)
and a better 5-year disease-free survival (63.8% vs
23.6%). Multivariate analysis suggested that a ≥65 µm
maximum diameter of the involved nerves was an
independent risk factor for both recurrence (P<0.001)
and gastric cancer-related death (P<0.001) within 5
years. However, if all patients were classified simply
based on whether PNI existed (regardless of the nerve size), this did not provide more information than
traditional clinicopathological variables. In conclusion,
the presence of cancer-involved nerves with a diameter
≥65 µm was a valuable prognostic factor for gastric
cancer.2015-01-01T00:00:00ZImmunohistochemical localization
of LLC1 in human tissues and its limited
expression in non-small cell lung cancerChandra, VishalChoi, Yong-BockHwang, Hai-LiLee, Jeong-HwaPark, Seong-YeolKim, Hyun-KyoungPoojan, ShivKoh, Jae-SooKim, Han-SeongHong, Kyeong-Manhttp://hdl.handle.net/10201/964642020-09-24T23:18:37Z2015-01-01T00:00:00ZTítulo: Immunohistochemical localization
of LLC1 in human tissues and its limited
expression in non-small cell lung cancer
Autor/es principal/es: Chandra, Vishal; Choi, Yong-Bock; Hwang, Hai-Li; Lee, Jeong-Hwa; Park, Seong-Yeol; Kim, Hyun-Kyoung; Poojan, Shiv; Koh, Jae-Soo; Kim, Han-Seong; Hong, Kyeong-Man
Resumen: We have shown both LLC1 expression in the
lung epithelium by in situ hybridization and its
inactivation in lung cancer by epigenetic modification.
However, LLC1 protein’s cellular localization or its role
in normal lung or cancer tissues has not yet been
evaluated. In the present study, a monoclonal antibody
against recombinant LLC1 was produced, and
immunohistochemical staining was performed on arrays
including various human tissues, normal lung and nonsmall cell lung cancer (NSCLC) tissues for LLC1
localization. The immunohistochemical results showed
LLC1 expression in the cilia of normal-airway epithelial
cells and in the cytoplasm of type II pneumocytes in
bronchiectatic patients, but no expression in most of the
NSCLC tissues, which is consistent with our previous
report positing LLC1 as a tumor suppressor. However,
LLC1 over-expression in NSCLC cell lines NCI-H1299
and NCI-H23 did not show any change in proliferation
or migration, which does not indicate any LLC1 tumorsuppressor role. As for the other human tissues, LLC1
was localized in renal tubular cells, pancreatic acinar
cells, and epithelial cells of the stomach, duodenum, and
gallbladder. In summary, our findings suggest that LLC1
is not a tumor suppressor, and that it is localized in the
cilia of the normal lung epithelium but is absent in most
NSCLC cases, probably due to the loss of cilia during
lung carcinogenesis.2015-01-01T00:00:00ZHistopathological findings in the
peritumoral edema area of human gliomaWang, XingfuLiu, XueyongChen, YupengLin, GuoshiMei, WenzhongChen, JianwuLiu, YingLin, ZhixiongZhang, Shenghttp://hdl.handle.net/10201/964632020-09-24T23:18:30Z2015-01-01T00:00:00ZTítulo: Histopathological findings in the
peritumoral edema area of human glioma
Autor/es principal/es: Wang, Xingfu; Liu, Xueyong; Chen, Yupeng; Lin, Guoshi; Mei, Wenzhong; Chen, Jianwu; Liu, Ying; Lin, Zhixiong; Zhang, Sheng
Resumen: Peritumoral brain edema (PTBE) is
considered to be one of the main biological behaviors of
brain glioma. However, the histopathological features of
PTBE remain imprecisely defined. We analyzed the
histopathological characteristics in the PTBE area of 22
cases of glioma. Microscopically, the pre-existing basic
structure in the edema area was still preserved but there
were varying degrees of loose tissue. The main
components of the edema tissue were scattered invasive
tumor cells, reactive cells, and various blood vessel
patterns. Invasive tumor cell density was significantly
higher in high-grade glioma than in low-grade glioma,
and the density was significantly higher in the area near
compared to the area far from the glioma. The Ki-67
proliferative index of the invasive tumor cells was higher
in high-grade glioma than in low-grade glioma, but the
index was not different in the area near compared to the
area far from the glioma. The microvessel pattern in
PTBE was primarily branching capillary. The
microvessel densities (MVDs) of CD34+ and CD105+
were higher in high-grade glioma and the area near the
glioma than in low-grade glioma and the area far from
the glioma. Compared to CD34+, the MVD of CD105+
exhibited a more significant downward trend in terms of
distance from the glioma. The most obvious types of reactive cells were reactive astrocytes and activated
microglia. The reactive astrocytes were positive for
nestin. The activated microglia emerged in the area near
the glioma in most cases and in the area far from the
glioma in more than half of the cases. In addition,
several cases displayed focal collections of small
lymphocytes around small blood vessels and tumor cells
arranged around a neuronal cell, and a limited number of
cases displayed giant dysmorphic neurons in an
edematous cortex. Our data indicate that PTBE is a
consequence of tissue reconstruction resulting from
tumor cell invasion and is an appropriate niche for the
growth and spread of glioma cells.2015-01-01T00:00:00Z