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NCI CANCERLIT® Search: Kidney (Renal Cell) Cancer - May 2002
National Cancer Institute®
Ultima Vez Modificado: 1 de mayo del 2002
Table of Contents
1
UI - 11762795
AU - Siebels M; Meyer G; Habicht A; Meuer SC; Moebius U
TI -
Simultaneous ligation of CD5 and CD28 with monoclonal antibodies
restores impaired immunostimulatory function in human renal cell
carcinoma.
SO - Urol Res 2001 Oct;29(5):330-7
AD - Research Group Gene Therapy of Tumors, German Cancer Research Center,
Heidelberg. siebels@uro.med.uni-muenchen.de
Tumor cells, including renal cell carcinoma (RCC) cells, do not
effectively stimulate T lymphocyte responses against specific antigens
presented on their surface. Reasons for this low immunogenicity may
include low or absent expression of MHC class I and/or class II
molecules, as well as accessory and costimulatory molecules. We used
tumor cell pretreatment with cytokines, together with monoclonal
antibodies (mAbs) directed at receptors for costimulatory molecules, to
render RCC cells immunostimulatory. Interferon-gamma or tumor necrosis
factor-alpha pretreatment enhanced expression of MHC class I and class
II molecules, as well as CD54, but had only minimal effects on T cell
activation. A CD28 mAb, or an even more effective combination of CD28
and CD5 mAb, induced strong primary proliferative responses of
allogeneic resting T lymphocytes. Cytokine pretreatment further
augmented this T cell response in vitro and allowed T cell expansion and
establishment of T cell lines. Stimulation of T cells with autologous
RCC cells resulted in a similar T cell activation but with the expansion
of cytolytic T cells directed at autologous MHC class II molecules.
These experiments demonstrate that cytokines combined with costimulatory
mAbs are useful for increasing the immunogenicity of tumor cells. They
also indicate. however, that autologous MHC class II expression on tumor
cells, together with strong costimulation, may lead to the activation of
autoreactive T cells.
2
UI - 11849447
AU - Horiguchi A; Oya M; Marumo K; Murai M
TI -
STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal
cancer cells, ACHN and 769P.
SO - Kidney Int 2002 Mar;61(3):926-38
AD - Department of Urology, Keio University School of Medicine, 35
Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
BACKGROUND: Although interleukin-6 (IL-6) has been suggested to function
as an autocrine growth factor in renal cell carcinoma (RCC), the
underlying mechanism responsible for the IL-6-induced proliferation of
RCC has not been defined. The aim of this study was to characterize the
signaling cascades mediating IL-6-induced proliferation and to
investigate the use of effective novel interventions to block the
IL-6-induced autocrine growth of renal cancer cells. METHODS:
IL-6-induced proliferation and intracellular signaling cascades were
analyzed in four human renal cancer cell lines Caki-1, ACHN, 769P and
A498. IL-6-induced activation of STAT3 (signal transducer and activator
of transcription-1) and extracellular signal-regulated kinases (ERKs),
and the effects of anti-IL-6 neutralizing antibody, Jak inhibitor AG
490, and MEK1 inhibitor PD 98059 were analyzed by Western blotting using
phospho-specific antibodies. The DNA-binding activities of STATs were
analyzed by EMSA. Apoptosis was determined by using nuclear staining and
the TUNEL assay. Changes in the apoptosis-related proteins, bcl-2,
bcl-xL, and bax were analyzed by Western blotting. RESULTS: IL-6 induced
tyrosine phosphorylation and increased the DNA binding activity of STAT3
and, to a lesser extent, STAT1 in all cell lines except for Caki-1,
which did not express the IL-6 receptor subunit gp130. ERKs were
constitutively activated in all cell lines and the activation level was
not up-regulated further by exogenously added IL-6 nor down-regulated by
anti-IL-6 neutralizing antibody. IL-6-induced STAT3 tyrosine
phosphorylation and DNA binding activity was inhibited by treatment with
Jak specific inhibitor AG 490; however, it was not affected by the MEK1
inhibitor PD 98059. Moreover, treatment with AG 490 inhibited
IL-6-induced proliferation of ACHN and 769P cells and induced apoptosis
with the down-regulation of bcl-2 and the up-regulation of bax.
CONCLUSIONS: This study identified STAT3, but not ERKs, to be a major
mediator of IL-6-induced proliferation of renal cancer cells. Although
ERKs were constitutively activated, ERKs were not found to be essential
for the IL-6-induced proliferation and modulation of the STAT3 activity.
Because the Jak specific inhibitor AG 490 effectively inhibited the
IL-6-induced STAT3 activity and induced apoptosis, the blockade of the
STAT3 signaling pathways is considered to be potentially useful as a
novel therapeutic approach for RCC.
3
UI - 11859199
AU - Amin MB; Amin MB; Tamboli P; Javidan J; Stricker H; de-Peralta Venturina
TI -
M; Deshpande A; Menon M
Prognostic impact of histologic subtyping of adult renal epithelial
neoplasms: an experience of 405 cases.
SO - Am J Surg Pathol 2002 Mar;26(3):281-91
AD - Department of Urology, Emory University School of Medicine, Atlanta,
Georgia 30322, USA. mahul_amin@emory.org
Just two and a half decades ago adult renal cell neoplasms, i.e., those
arising from the renal tubules or collecting duct epithelium, were
subdivided into two major subtypes: "clear cell carcinoma" and "granular
cell carcinoma." Subsequent detailed morphologic and/or cytogenetic
studies have resulted in the recognition of several distinctive subtypes
of adult renal epithelial neoplasms, which has led to the promulgation
of a refined contemporary histologic classification of these tumors.
This study examines the prognostic significance of histologic subtyping
in accordance with the new classification in a consecutive series of 405
cases treated at a single institution. Cases were histologically
classified into 28 (7%) benign tumors [27 (6.7%) renal oncocytomas, 1
(0.2%) metanephric adenoma] and 377 (93%) malignant tumors [255 (63%)
conventional (clear cell) renal cell carcinoma, 75 (18.5%) papillary
renal cell carcinoma, 24 (5.9%) chromophobe renal cell carcinoma, and 23
(5.7%) renal cell carcinoma, unclassified]. A total of 25 (6.6%)
malignant tumors showed evidence of sarcomatoid change. Kaplan-Meier
survival analysis with log-rank test showed histologic type (p = 0.002),
Fuhrman's nuclear grade (p = 0.001), TNM stage (p = 0.001), vascular
invasion (p = 0.001), and necrosis (p = 0.001) to be significantly
associated with disease-specific survival and progression-free survival,
based on follow-up of 368 patients (mean 64.5 months, median 56 months).
The 5-year disease-specific survival for chromophobe renal cell
carcinoma, papillary renal cell carcinoma, conventional (clear cell)
renal cell carcinoma, and renal cell carcinoma, unclassified was 100%,
86%, 76%, and 24%, respectively; no patient with a benign tumor
diagnosis progressed or died of disease. The 5-year progression-free
survival for chromophobe renal cell carcinoma, papillary renal cell
carcinoma, conventional (clear cell) renal cell carcinoma, and renal
cell carcinoma, unclassified was 94%, 88%, 70%, and 18%, respectively.
Malignant tumors with sarcomatoid change had a 35% and 27%, 5-year
disease-specific and progression-free survival, respectively. Cox
proportional hazards regression analysis showed TNM stage (p = 0.001),
nuclear grade (p = 0.01), and necrosis (p = 0.05) to be significant
predictors of disease-specific survival. In conclusion, our study shows
that the histologic categorization of adult renal epithelial neoplasms
performed by routine light microscopic hematoxylin and eosin-based
examination in accordance with the contemporary classification scheme
has prognostic utility.
4
UI - 11993207
AU - Murota T; Danno S; Oguchi N; Shimada O; Nakagawa M; Sugi M; Muguruma K;
TI -
Koyama Y; Kawamura H; Ohara T; Kawakita M; Matsuda T
[The experience of laparoscopic radical nephrectomy for renal tumors]
SO - Hinyokika Kiyo 2002 Mar;48(3):145-50
AD - Department of Urology, Kansai Medical University.
We evaluate the safety and feasibility of laparoscopic radical
18 patients with renal tumors underwent laparoscopic radical
nephrectomy. The mean patient age was 57.1 years ranging from 36 to 78.
Clinical stage was T1N0 in all patients. The mean tumor diameter was 4.0
cm ranging from 1.8 to 7.0. Laparoscopic radical nephrectomy was
performed by using the transperitoneal anterior approach on 11 patients
and retroperitoneal approach on 7 patients. The specimen was removed
through an extended stab wound after blunt segmentation of renal
parenchyma in a specimen bag (LapSac). The mean operative time was 405
(270-550) and 453 (325-635) min for the transperitoneal approach and
retroperitoneal approach respectively, and the mean blood loss was 281
(52-700) and 223 (10-850) ml, respectively. There was an intraoperative
complication of minor splenic injury in 2 patients receiving the
transperitoneal approach, which was conservatively managed.
Histopathology revealed renal cell carcinoma in 17 patients and renal
oncocytoma in one patient. There was no recurrence with a mean follow-up
of 28.9 months. Compared with 13 patients who underwent open radical
nephrectomy during the same period, laparoscopic nephrectomy has a
longer operative time (424 versus 214 min, p < 0.001), equal blood loss
(259 versus 210 ml, p = 0.59), quicker resumption of ambulation (1.8
versus 2.5 days, p = 0.016) and food intake (1.4 versus 2.2 days, p =
0.003), shorter postoperative hospital stay (10.9 versus 18 days, p =
0.0016), and a tendency of less frequent analgesic requirements (1.9
versus 4.7 times, p = 0.09). Laparoscopic radical nephrectomy is a safe
and useful surgery for renal tumors providing minimal invasiveness.
5
UI - 11943130
AU - Kaplan S; Ekici S; Dogan R; Demircin M; Ozen H; Pasaoglu I
TI -
Surgical management of renal cell carcinoma with inferior vena cava
tumor thrombus.
SO - Am J Surg 2002 Mar;183(3):292-9
AD - Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine,
Hacettepe University, Ankara, Turkey. skaplan@bir.net.tr
BACKGROUND: The successful excision of a renal cell carcinoma (RCC)
invading the inferior vena cava (IVC) remains a technical intraoperative
challenge and requires a careful preoperative surgical management
planning. Although a radical operation remains the mainstay of the
therapy for RCC, the optimal management of the patients with RCC causing
IVC tumor thrombus remains unresolved. In this study, we reviewed our
experience in this group of patients and herein report the results.
IVC tumor thrombus underwent surgical treatment. The mean patient age
was 54.2 years and the male to female ratio was 1.75. The cephalad
extension of the tumor was suprarenal in all cases, being infrahepatic
in 6 patients, intrahepatic in 2, and suprahepatic with right atrial
extension in 3 patients. All tumors were resected via inferior vena cava
isolation and, when necessary, extended hepatic mobilization and Pringle
maneuver, with primary or patch closure of vena cavotomy.
Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest
(DHCA) were used in 3 patients. RESULTS: The mortality rate was 9.1% (1
patient was lost on the 11th postoperative day). Complications occurred
in 3 patients. The remaining 10 patients (90.9%) could be successfully
discharged from hospital. Two of them were lost during follow-up because
of tumor progression at the 43rd and 54th postoperative months. The
10-year Kaplan-Meier survival estimate was 71.4%, with a mean follow-up
of 4.6 years. The presence of lymph node metastases and perinephric
spread seemed to possess an adverse effect on the survival. Although the
groups included small numbers of patients, there was no significant
difference in survival in regard to the different levels of tumor
thrombus extension into the vena cava. CONCLUSIONS: Surgical treatment
is the preferred approach to patients with RCC and IVC tumor thrombi as
it provides markedly better results when compared with the other
therapeutical modalities. We believe that complete surgical excision of
the tumor and the resulting thrombus with appropriate preoperative
staging and a well-planned surgical approach, using CPB and DHCA when
necessary, provide an acceptable long-term survival with a good quality
of life expectation.
6
UI - 10210376
AU - Walther MM; Choyke PL; Glenn G; Lyne JC; Rayford W; Venzon D; Linehan WM
TI -
Renal cancer in families with hereditary renal cancer: prospective
analysis of a tumor size threshold for renal parenchymal sparing
surgery.
SO - J Urol 1999 May;161(5):1475-9
AD - Urologic Oncology Branch, Department of Radiology, National Cancer
Institute, National Institutes of Health, Bethesda, Maryland, USA.
PURPOSE: Patients with hereditary forms of renal cancer are at risk for
new tumors and metastases. Renal parenchymal sparing surgery has been
performed to preserve renal function and quality of life, and prevent
metastases. We evaluated a 3 cm. threshold for performing renal
parenchymal sparing surgery in patients with von Hippel-Lindau disease
and hereditary papillary renal cancer. MATERIALS AND METHODS: Patients
with von Hippel-Lindau disease or hereditary papillary renal cancer and
renal cancer were identified by screening affected kindred and by
kindred history. Patients with small tumors were followed with serial
imaging studies until the largest renal tumor was 3 cm., when renal
parenchymal sparing surgery was performed. Renal tumors greater than 3
cm. were resected without delay. Parenchymal sparing techniques were
used when possible in each group. RESULTS: The 3 cm. surgical threshold
was evaluated in 52 patients with von Hippel-Lindau disease (group 1) at
a median followup of 60 months (range 6 to 205). None of these patients
had metastatic disease and none has required renal transplantation or
dialysis. In 44 patients with von Hippel-Lindau disease (group 2) renal
tumors larger than 3 cm. developed. Median followup from the initial
radiological diagnosis of renal cancer in this group was 66.5 months
(range 0 to 321). Patients in group 1 underwent parenchymal sparing
surgery instead of nephrectomy more frequently than those in group 2 (46
of 48 operations or 96% versus 45 of 72 or 63%, Fisher's exact test p
<0.0001). In contrast to patients in group 1, metastatic renal cancer
developed in 11 of the 44 in group 2 (25%) (Fisher's exact test p
<0.0001). A total of 23 patients with hereditary papillary renal cancer
were also identified. Median followup in these cases was 44 months
(range 0 to 237). Ten patients had tumors less than 3 cm. No patient
with tumors less than 3 cm. and 2 of the 13 (15%) with larger tumors had
metastases. CONCLUSIONS: Using a 3 cm. renal tumor diameter as an
indication for renal surgery no patient with renal cancer and von
Hippel-Lindau disease or hereditary papillary renal cancer had
metastatic disease regardless of the number of tumors. Using a lesion
size of 3 cm. as a threshold for performing renal parenchymal sparing
surgery may help to prevent metastatic disease, unnecessary renal damage
due to frequent surgery and renal dialysis or transplantation.
7
UI - 11549509
AU - Haitel A; Wiener HG; Neudert B; Marberger M; Susani M
TI -
Expression of the cell cycle proteins p21, p27, and pRb in clear cell
renal cell carcinoma and their prognostic significance.
SO - Urology 2001 Sep;58(3):477-81
AD - Department of Pathology, University of Vienna, Vienna, Austria.
OBJECTIVES: To determine whether p21, p27, and pRb can predict disease
progression in clear cell renal cell carcinoma. METHODS: The expression
of three negative regulators of the cell cycle, the retinoblastoma gene
product (pRb), the WAF1/Cip1 gene product (p21), and the Kip1 gene
product (p27), was investigated by immunohistochemistry on paraffin
sections from 104 formalin-fixed clear cell carcinoma specimens and
related to p53 overexpression, the clinicopathologic parameters, and
survival. RESULTS: pRb expression was not associated with tumor stage,
but the correlation with p27 and p21 positivity was statistically
significant (r = 0.26, P = 0.008 and r = 0.3, P = 0.002, respectively).
Tumors representing p53 overexpression showed a higher pRb labeling
index compared with p53-negative tumors (P = 0.0004). p21 protein
expression correlated significantly with p27 positivity (r = 0.2, P =
0.04) and was associated with p53 overexpression (P = 0.0005), but did
not correlate with tumor stage or grade. No association could be found
between p27 positivity and tumor grade, tumor stage, or p53
overexpression. In univariate survival analysis, an increased pRb
positivity (P = 0.002) and a low p27 expression (P = 0.0001) predicted a
poor outcome, especially if combined with p53 overexpression (P = 0.004
and P = 0.0002, respectively). p21 did not give any prognostic
information. Moreover, in multivariate analysis, pRb and p27 were
revealed to be statistically significant. CONCLUSIONS: The results of
our study indicate that in clear cell renal cell carcinoma, the cell
cycle proteins p27 and pRb are powerful and independent prognostic
factors and that p21 has no predictive value.
8
UI - 11586243
AU - Walther MM; Pautler S
TI -
Re: von Hippel-Lindau disease: renal tumors less than 3 cm. can
metastasize.
SO - J Urol 2001 Nov;166(5):1837
9
UI - 11977630
AU - Zheng J; Sun X; Chen J; Jiang F; Li W; Xie S
TI -
[Mechanism of immune escape in renal cell carcinoma]
SO - Zhonghua Zhong Liu Za Zhi 2002 Jan;24(1):24-6
AD - Department of Urology, Xuzhou Medical College Hospital, Xuzhou 221002,
China.
OBJECTIVE: To investigate the mechanism of immune escape in renal cell
carcinoma(RCC). METHODS: Fas and FasL expressions were examined by
immunohistochemical technique in 44 RCC patients, with the Ki67
expression and apoptosis of tumor infiltrating lymphocytes(TIL)
monitored simultaneously. Cytokines including IL2 and IFN alpha were
used to induce the expression of the renal carcinoma cell lines 786-0
cells. Combination treatment of 786-0 with cytokines and Anti-Fas
monoclonal antibody (FasAb) was used to induce apoptosis. FasL function
was assessed by in vitro co-culture assays using renal cancer cells
786-0 and Fas-sensitive Jurkat T-cells. RESULTS: (1) Fas expression rate
in RCC(22.8%) was lower than that in the controlled normal kidney
tissues(53.8%, P < 0.01). FasL expression rate in RCC (46.5%) was higher
than that in the controlled normal kidney tissues (23.2%, P < 0.01).
That of Ki67 was 32.8%, with the expressions of Fas and Ki67 showing a
negative correlation (r = -0.62, P < 0.05). In contrast, the expressions
of FasL and Ki67 showed a positive correlation. (r = 0.93, P < 0.01).
The Fas expression of stage I was significantly higher than that of
stages III and IV. The expression rate of FasL in RCC was significantly
increased with RCC stage (P < 0.01). (2) The apoptotic rate of TIL in
RCC (33.9%) was significantly higher than that of the normal kidney
tissues (3.5%, P < 0.01). The expression of FasL and the apoptotic rate
of TIL in RCC gave a positive correlation (r = 0.96, P < 0.01). (3) Fas
expression rate in 786-0 cells was 13.7%. The apoptotic rate mediated by
FAsAb was 9.6%. IFN alpha was able to up-regulate the Fas expression and
subsequently augment the FasAb-mediated apoptosis in 786-0 cells. But
IL2 did not show similar effects. (4) The FasL expression rate of 786-0
was 18.6%. FasL expressed by 786-0 cells was able to induce apoptosis of
Jurkat T-cells in co-culture assays and the apoptosis of Jurkat T-cells
was significantly lowered after blocking the effect of FasL with
Fas-neutralizing antibody NOK-2, giving the apoptotic rates of 14.9% and
2.0%, respectively, the difference therein is statistically significant
(P < 0.01). CONCLUSION: Down-regulation of Fas expression and
up-regulation of FasL-expression are the mechanisms through which the
RCC cells escape from immune attack.
10
UI - 11996794
AU - Dal Cin P; Sciot R; Van Poppel H; Balzarini P; Roskams T; Van den Berghe
TI -
H
Chromosome changes in sarcomatoid renal carcinomas are different from
those in renal cell carcinomas.
SO - Cancer Genet Cytogenet 2002 Apr 1;134(1):38-40
AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical
School, Brookline Avenue, Boston, MA, USA. pdalcin@partners.org
Sarcomatoid renal carcinoma (SRC) is an uncommon and highly malignant
renal tumor with sarcomatous morphology or with both sarcomatous and
carcinomatous components. The tumors are generally referred to as
dedifferentiated or transformed renal cell carcinomas (RCC). Information
on their genomic changes is scarce. Data from a cytogenetic study of
four cases of SRC are presented in this article. Combined with a few
other cases from the literature, it appears that genomic changes in most
cases of SRC have little in common with those characterizing
conventional RCC. Sarcomatoid transformation thus may occur occasionally
in RCC without the characteristic chromosome changes but also, and
perhaps more frequently, in a subgroup of RCC without the characteristic
chromosome changes.
11
UI - 11996788
AU - Bodmer D; Eleveld M; Ligtenberg M; Weterman M; van der Meijden A; Koolen
TI -
M; Hulsbergen-van der Kaa C; Smits A; Smeets D; Geurts van Kessel A
Cytogenetic and molecular analysis of early stage renal cell carcinomas
in a family with a translocation (2;3)(q35;q21).
SO - Cancer Genet Cytogenet 2002 Apr 1;134(1):6-12
AD - Department of Human Genetics, University Medical Center Nijmegen, PO Box
9101, 6500 HB Nijmegen, The Netherlands. d.bodmer@antrg.azn.nl
Previously, we described a family with renal cell carcinoma (RCC) and a
constitutional balanced t(2;3) (q35;q21). Based on loss of
heterozygosity and von Hippel-Lindau (VHL) gene mutation analyses in
five tumor biopsies from three patients in this family, we proposed a
multistep model for RCC development in which the familial translocation
may act as a primary oncogenic event leading to (nondisjunctional) loss
of the translocation-derived chromosome 3, and somatic mutation of the
VHL gene as a secondary event related to tumor progression. Here, we
describe the cytogenetic and molecular analysis of three novel tumors at
early stages of development in two members of this family. Again, loss
of derivative chromosome 3 was found in two of these tumors and a VHL
mutation in one of them. In the third tumor, however, none of these
abnormalities could be detected. These results underline our previous
notion that loss of derivative chromosome 3 and VHL gene mutation play
critical roles in familial RCC. In addition, they show that both
anomalies may occur at relatively early stages of tumor development.
12
UI - 11840554
AU - Sullentrop F; Moka D; Neubauer S; Haupt G; Engelmann U; Hahn J; Schicha
TI -
H
31P NMR spectroscopy of blood plasma: determination and quantification
of phospholipid classes in patients with renal cell carcinoma.
SO - NMR Biomed 2002 Feb;15(1):60-8
AD - Institute of Inorganic Chemistry, University of Cologne, Cologne,
Germany.
Advanced renal cell carcinoma (RCC) has a poor prognosis and is
characterized by an unpredictable clinical course. The aim of this study
was to assess the systemic phospholipid distribution as a possible
marker of tumor stage and tumor spread beyond the kidney. To this end,
the effect of renal cell carcinoma (RCC) on phospholipid concentrations
in blood plasma using 31P NMR spectroscopy was studied in: (a) 29
patients with RCC prior to nephrectomy; (b) 19 healthy volunteers; (c)
three patients with other renal tumors (renal metastases of bronchial
carcinoma and of renal pelvic carcinoma, and a benign renal tumor).
Furthermore, the phospholipid concentrations of eight patients of group
(a) were determined 6 months after nephrectomy, when they were in
remission. We found considerable deviations in the concentrations of the
lysophosphatidylcholines (LPC1, LPC2) in both male and female patients
with RCC compared to healthy volunteers (male--LPC1 0.217+/-0.062 vs
0.297+/-0.049 mmol/l, LPC2 0.036+/-0.014 vs 0.068+/-0.024 mmol/l;
female--LPC1 0.195+/-0.071 vs 0.296+/-0.044 mmol/l, LPC2 0.037+/-0.027
vs 0.044+/-0.014 mmol/l). In addition, female patients with RCC showed
lower concentrations of phosphatidylcholines (PC; 1.409+/-0.268 vs
1.947+/-0.259 mmol/l). The low phospholipid concentrations normalized
for patients in remission. Phospholipid concentrations were found to
depend on tumor stage and metastatic spread. The deviations in
phospholipid concentrations (LPC1, LPC2, PC) observed may be
attributable to systemic effects caused by the tumor as well as changes
in enzyme activities. Copyright 2002 John Wiley & Sons, Ltd.
13
UI - 11804384
AU - Bertetto O; Bracada S; Tamburini M; Cortesi E
TI -
Quality of life studies and genito-urinary tumors.
SO - Ann Oncol 2001;12 Suppl 3():S43-8
AD - Medical Oncology Division, Le Molinette Hospital, Turin, Italy.
BACKGROUND: Genitourinary (GU) tumors represent a large proportion of
solid cancers (1 of 4) and a wide variety of natural histories, based on
various prognostic factors and resulting in different treatment options
and end points. In some cases, for the same stage of disease, different
treatment strategies do not impact differently on overall survival (OS):
surgery vs. radiation, or radical vs. conservative multidisciplinary
approach, adjuvant or neoadjuvant, chemotherapy vs. BSC. Quality of life
(QoL) is considered a reasonable end point when differences in OS do not
seem to be striking. DESIGN: A review of the literature on different
disease stages was undertaken to show where and when QoL was used as the
end point of treatment efficacy. RESULTS: Very few studies have been
performed in prostate, bladder and testicular cancer to show the impact
of different treatment approaches on QoL. Although these studies might
be considered as non-conclusive, some data may allow a better choice for
the patients. CONCLUSIONS: QoL as the principal end point has not been
used in clinical trials of GU tumors comparing different treatment
approaches. This makes the choice between treatments offering similar
survival but different toxicity patterns, body and behavioral
consequences more difficult. We suggest that future prospective
randomized studies should be planned taking into account the QoL as the
main end point.
14
UI - 11865331
AU - Nikiforova NV; Khodyreva LA; Kirpatovskii VI; Chumakov AM
TI -
Lipid peroxidation in malignant tumors of human kidneys.
SO - Bull Exp Biol Med 2001 Nov;132(5):1096-9
AD - Institute of Urology, Ministry of Health of Russian Federation, Moscow.
The intensity of ascorbate-dependent free radical oxidation of
endogenous lipids in malignant tumor tissue of human kidneys was
studied. The LPO induction period was markedly increased in renal-cell
carcinoma and malignant mesenchymal tumors compared to normal renal
cortex. The content of alpha-tocopherol in cancer tissue lipids was
considerably (7-fold) increased compared to that in normal renal cortex,
which explains high antioxidant activity of these carcinomas. A less
pronounced increase in the content of alpha -tocopherol in lipids of
malignant mesenchymal tumors compared to the cortex (2-fold) can also
contribute to their LPO resistance.
15
UI - 11963303
AU - Huttemann E; Schelenz C; Franke U; Schlichter A; Reinhart K
TI -
[Transesophageal echocardiography and intraoperative management of
patients with renal cell carcinoma and rena cava extension]
SO - Anaesthesist 2002 Feb;51(2):116-9
AD - Klinik fur Anasthesiologie und Intensivtherapie, Universitatskliniken,
Friedrich-Schiller-Universitat Jena. Egbert.Huettemann@med.uni-jena.de
OBJECTIVE: To evaluate the role of intraoperative real-time
transesophageal echocardiography (TEE) for the anesthetic and surgical
management of patients with renal cell carcinoma and vena cava
extension. METHODS: Retrospective analysis of the intraoperative
application of TEE in a series of 4 patients. RESULTS: Real-time TEE
with a multiplane probe allowed visualization of inferior vena cava
tumor extensions, accurate assessment of the distal extent of vena cava
invasion into hepatic veins and right atrium, monitoring of embolism and
evaluation of cardiac preload and function in all patients. CONCLUSION:
Intraoperative TEE is a useful adjunct to the anesthetic and surgical
management of patients with renal cell carcinoma and vena cava
extension.
16
UI - 11996245
AU - Piltz S; Meimarakis G; Wichmann MW; Hatz R; Schildberg FW; Fuerst H
TI -
Long-term results after pulmonary resection of renal cell carcinoma
metastases.
SO - Ann Thorac Surg 2002 Apr;73(4):1082-7
AD - Department of Surgery and Thoracic Surgery, Klinikum Grosshadern,
Ludwig-Maximilians-University Munich, Germany.
spiltz@gch.med.uni-muenchen.de
BACKGROUND: Until now no conclusive data exist regarding the factors
influencing long-term survival after pulmonary resection of renal cell
carcinoma metastases. The aim of the present study, therefore, was to
discover definitive prognostic factors for survival using a large and
homogeneous single center patient cohort. METHODS: Between 1980 and
2000, 105 patients, after curative resection of lung metastases from
renal cell carcinoma, were followed in this long-term study. These
patients underwent a total of 150 surgical procedures. Survival analysis
was done using the Kaplan-Meier method and the log-rank test.
Multivariate analysis of prognostic factors was performed using the Cox
multivariate proportional hazard model. RESULTS: Median survival after
curative resection reached 43 months (range, 1 to 218 months). Survival
at 3, 5, and 10 years was 54%, 40%, and 33%, respectively. Univariate
analysis revealed that a complete resection, a less than 4-cm diameter
of the metastases and tumor-free lymph nodes at the time of primary
operation, were highly significant dependent prognostic factors (p <
0.001). These factors were also shown to be independent prognostic
factors as suggested by multivariate analysis (p < 0.05). CONCLUSIONS:
The size of the metastatic nodule, the completeness of pulmonary
resection, and the lymph node status at the time of nephrectomy are the
most important prognostic factors that influence survival after
resection of pulmonary metastases. Recurrence of resectable pulmonary
metastases does not impair survival, thus favoring repeated resection in
patients with recurrent disease.
17
UI - 11995271
AU - Lee F; Patel HR
TI -
Kidney cancer: current management guidelines.
SO - Hosp Med 2002 Apr;63(4):214-7
AD - Institute of Urology and Nephrology, University College London, London
W1W 7EY.
Renal cell carcinoma accounts for 2% of all cancers. Medical progress
has improved the outcome of early but not advanced disease. This article
highlights the current practice for the management of renal cell
carcinoma.
18
UI - 11880110
AU - Chuanzhong Y; Ming G; Fanglin Z; Haijiao C; Zhen L; Shiping C; YongKang
TI -
Z
Real-time quantitative reverse transcription-PCR assay for renal cell
carcinoma-associated antigen G250.
SO - Clin Chim Acta 2002 Apr;318(1-2):33-40
AD - Department of Urology, Zhong shan Hospital, Medical Center of Fudan
University, 180 Feng lin Road, Shanghai 200032, People's Republic of
China. chuanzhong@mycity.com.cn
OBJECTIVES: Gene amplification/expression of G250 is a major event in
human renal tumorigenesis. G250-based therapeutic agents and
G250-specific gene therapy are under development. These new perspectives
call for a sensitive and accurate method to screen G250 alterations in
renal cell cancer (RCC) patients and investigate the relationship
between G250 mRNA expression and RCC. METHODS: We developed a
quantitative RT-PCR assay for the measurement of G250 mRNA expression
using a real-time procedure based on the use of fluorogenic probes and
the ABI PRISM 7700 Sequence Detector System. The method has been applied
to the measurement of quantitative mRNA level of G250 in 31 cases RCC
and 6 normal renal tissues. RESULTS: The dynamic range was 10(3)-10(8).
The relationship between Ct and log starting concentration was linear
(r=0.99). G250 expression was present in all RCCs with G250
amplification but was absent in normal ones. G250 mRNA expression ranged
from 2.9 x 10(3) to 6.5 x 10(7) copy/microg RNA, with a mean value of
3.5 x 10(6) copy/microg RNA. The expression of G250 revealed an inverse
correlation to tumor grade. G250 mRNA level did not correlate with the
cell types and clinical stages (P>0.05). CONCLUSIONS: G250 has the
potential to be used as a marker of diagnosis and increasing
proliferation in RCC. This new simple, rapid, semi-automated assay was a
major alternative to competitive PCR and Northern blot analysis for gene
alteration analysis in human tumors and might be a powerful tool for
large randomized, prospective cooperative group trials and supporting
future G250-based biological and gene therapy approaches.
19
UI - 11896565
AU - Izumi H; Hara T; Oga A; Matsuda K; Sato Y; Naito K; Sasaki K
TI -
High telomerase activity correlates with the stabilities of genome and
DNA ploidy in renal cell carcinoma.
SO - Neoplasia 2002 Mar-Apr;4(2):103-11
AD - hidequi@aol.comDepartment of Pathology, Yamaguchi University School of
Medicine, 1-1-1, Minami Kogushi, Ube-city, Yamaguchi, 755-8505, Japan.
Malignant tumors have telomerase activity, which is thought to play a
critical role in tumor growth. However, the relation between telomerase
activity and genomic DNA status in tumor cells is poorly understood. In
the present study, we examined telomerase activity in 13 clear cell type
renal cell carcinomas (CRCCs) with similar clinicopathologic features by
telomeric repeat amplification protocol assay (TRAP). Based on TRAP
assay results, we divided the CRCCs into two groups: a high telomerase
activity group and a low/no telomerase activity group. We then analyzed
genomic aberration, DNA ploidy, and telomere status in these two groups
by comparative genomic hybridization (CGH), laser scanning cytometry
(LSC), and telomere-specific fluorescence in situ hybridization
(T-FISH), respectively. CGH showed the high telomerase activity group to
have fewer genomic changes than the low/no telomerase activity group,
which had many genomic aberrations. Moreover, with LSC, DNA diploid
cells were found more frequently in the high telomerase activity group
than in the low/no telomerase activity group. In addition, T-FISH
revealed strong telomere signal intensity in the high telomerase
activity group compared with that of the low/no telomerase activity
group. These results suggest that telomerase activity is linked to
genomic DNA status and that high telomerase activity is associated with
genomic stability, DNA ploidy, and telomere length in CRCC.
20
UI - 11914915
AU - Vis N; van der Gaast A; van Rhijn G; Catsburg K; Schmidt C; Mickisch J
TI -
A phase II trial of methotrexate-human serum albumin (MTX-HSA) in
patients with metastatic renal cell carcinoma who progressed under
immunotherapy.
SO - Cancer Chemother Pharmacol 2002 Apr;49(4):342-5
AD - Department of Urology, Academic Hospital Rotterdam, Erasmus University
Rotterdam, 3015 GD Rotterdam, The Netherlands.
INTRODUCTION: Renal cell carcinoma (RCC) has a poor prognosis when
metastasized to distant sites, although immunotherapy may offer a
prolongation of survival in selected patient groups. Unfortunately, no
treatment options remain when immunotherapy fails. In this phase IIa
trial the tolerability and efficacy of the antifolate drug
methotrexate-human serum albumin (MTX-HSA) were evaluated in patients
with metastatic RCC who progressed after first-line immunotherapy.
PATIENTS AND METHODS: A total of 17 patients started treatment, and 14
(12 men, 2 women) were evaluable for response according to the phase IIa
Gehan design. Patients had had prior tumor nephrectomy, were in
relatively good general condition, had no impairment of renal, liver or
bone marrow function, and had progressive metastatic disease after
treatment with interferon-alpha (IFN-alpha) with or without cis-retinoic
acid (EORTC protocols 30951 and 30947). MTX-HSA was given once a week
intravenously on an outpatient basis at a dose of 50 mg/m(2). The
treatment interval was prolonged in those patients who had not yet
recovered from previous toxicities. RESULTS: Toxicity was manageable,
relatively mild to moderate and reversible in most cases. Grade 2/3
mucositis (10/17) and grade 3 elevated transaminase levels (4/17) were
most frequent, and in only one patient was a grade 4 thrombocytopenia
reported. Of three inevaluable patients, one discontinued treatment due
to drug-related toxicities. The mean administration interval was 12.1
days, and 7 of 14 evaluable patients had treatment intervals of 1 or 2
weeks. No objective responses were seen, although eight patients had
stable disease (stabilization >2 months) for up to 8 months (median 121
days). CONCLUSION: MTX-HSA was generally well tolerated and can be given
on an outpatient basis, but no objective responses were seen in patients
with metastatic RCC who had progressed after previous immunotherapy.
21
UI - 11929471
AU - Mickisch GH
TI -
Principles of nephrectomy for malignant disease.
SO - BJU Int 2002 Mar;89(5):488-95
AD - Department of Urology, Erasmus University and Academic Hospital,
Rotterdam, The Netherlands. mickisch@urol.azr.nl
For many years the prevailing belief was to advocate'radical'
nephrectomy via a transperitoneal approach as the standard surgical
procedure for renal cell carcinoma (RCC). because the early control of
the renal vessels before manipulating the kidney should minimize the
likelihood of disseminating tumour cells during surgery.This philosophy
was based on retrospective data which were never confirmed in a
controlled trial. Since then,evidence has accumulated that some patients
maybe better served by an extraperitoneal (translumbar)approach,
providing similar oncological efficacy with the added advantage of
reduced morbidity. However,these results are again either retrospective
or statistically insignificant, and therefore do not allow firm
conclusions. Nevertheless, if there is any difference in the possible
intraoperative dissemination of tumour, depending on the type of
surgical approach, it will be small, requiring analysis in a large
randomized multicentre trial. The treatment of choice for disease that
is not disseminated is surgery, although the 5-year survival rates for
all stages do not exceed 60%, even in contemporary series. Further
improvements will probably have to rely on the development of more
effective systemic therapy and the application of combined treatments to
counter the relatively many patients presenting with advanced stages.
Concepts and progress in this field appear to be of major interest for
modern uro-oncologists after the advent of immunotherapeutic strategies
that require a surgical intervention at some stage of the treatment
cascade.
22
UI - 11953881
AU - Schrader AJ; Lechner O; Templin M; Dittmar KE; Machtens S; Mengel M;
TI -
Probst-Kepper M; Franzke A; Wollensak T; Gatzlaff P; Atzpodien J; Buer
J; Lauber J
CXCR4/CXCL12 expression and signalling in kidney cancer.
SO - Br J Cancer 2002 Apr 22;86(8):1250-6
AD - Department of Cell Biology and Immunology, German Research Centre for
Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany.
CXCL12 (SDF-1), a CXC-chemokine, and its specific receptor, CXCR4, have
recently been shown to be involved in tumourgenesis, proliferation and
angiogenesis. Therefore, we analysed CXCL12alpha/CXCR4 expression and
function in four human kidney cancer cell lines (A-498, CAKI-1, CAKI-2,
HA-7), 10 freshly harvested human tumour samples and corresponding
normal kidney tissue. While none of the analysed tumour cell lines
expressed CXCL12alpha, A-498 cells were found to express CXCR4. More
importantly, real-time RT-PCR analysis of 10 tumour samples and
respective adjacent normal kidney tissue disclosed a distinct and
divergent downregulation of CXCL12alpha and upregulation of CXCR4 in
primary tumour tissue. To prove that the CXCR4 protein is functionally
active, rhCXCL12alpha was investigated for its ability to induce changes
of intracellular calcium levels in A-498 cells. Moreover, we used cDNA
expression arrays to evaluate the biological influence of CXCL12alpha.
Comparing gene expression profiles in rhCXCL12alpha stimulated vs
unstimulated A-498 kidney cancer cells revealed specific regulation of
31 out of 1176 genes tested on a selected human cancer array, with a
prominent stimulation of genes involved in cell-cycle regulation and
apoptosis. The genetic changes reported here should provide new insights
into the developmental paths leading to tumour progression and may also
aid the design of new approaches to therapeutic intervention. Copyright
2002 Cancer Research UK
23
UI - 11990825
AU - Rosahl SK; Roser F; Samii M
TI -
Renal metastasis.
SO - J Neurosurg 2002 Apr;96(4):804-5; discussion 805
24
UI - 11992832
AU - Chao DH; Zisman A; Pantuck AJ; Freedland SJ; Said JW; Belldegrun AS
TI -
Changing concepts in the management of renal oncocytoma.
SO - Urology 2002 May;59(5):635-42
AD - Division of Urologic Oncology, Department of Urology, University of
California, Los Angeles, School of Medicine, Los Angeles, California
90095-1738 , USA
25
UI - 11992840
AU - Yang MH; Chen KK; Yen CC; Wang WS; Chang YH; Huang WJ; Fan FS; Chiou TJ;
TI -
Liu JH; Chen PM
Unusually high incidence of upper urinary tract urothelial carcinoma in
Taiwan.
SO - Urology 2002 May;59(5):681-7
AD - Division of Medical Oncology, Department of Medicine, Taipei Veterans
General Hospital and National Yang-Ming University School of Medicine,
Taipei, Taiwan, Republic of China.
OBJECTIVES: Unusually high incidences of upper urinary tract urothelial
carcinoma (UUT-UC) have been reported from the endemic area for
"blackfoot disease" of southern Taiwan, and the arsenic-contaminated
water was considered to be the reason for this prevalence. In this
study, we determined the ratio of UC in different locations, the
difference in clinical profiles for UUT-UC and urinary-bladder
urothelial carcinoma (UB-UC), and the influence of tumor location on
survival in a medical center of northern Taiwan. METHODS: A total of 535
patients with pathologically proven UC were reviewed retrospectively in
this study, and clinical data were recorded from pathologic and chart
reviews. Statistical analyses to determine the association between tumor
location and clinical variables, and stratified survival analyses to
determine the effect of tumor location on survival were performed.
RESULTS: The incidence of UUT-UC was relatively high (the ratio of renal
pelvis/ureter/urinary bladder was 1:2.08:6.72), even though most of the
patients did not reside in the endemic "blackfoot disease" area. Young
age, female sex, higher T stage, and elevated pretreatment serum lactate
dehydrogenase and creatinine level were significantly associated with
UUT-UC after multivariate logistic regression analysis. Tumor location
influenced survival in patients with early-stage disease or favorable
prognostic factors. CONCLUSIONS: Factors other than arsenic water
contamination may contribute to the unusually high incidence of UUT-UC
in the non-"blackfoot disease" area in Taiwan. UUT-UC carried a more
aggressively clinical behavior than UB-UC; tumor location influences
patient survival markedly in patients with early-stage disease or
favorable prognostic factors.
26
UI - 11920739
AU - Ramp U; Caliskan E; Ebert T; Karagiannidis C; Willers R; Gabbert HE;
TI -
Gerharz CD
FHIT expression in clear cell renal carcinomas: versatility of protein
levels and correlation with survival.
SO - J Pathol 2002 Apr;196(4):430-6
AD - Institute of Pathology, Heinrich Heine University, 40225 Duesseldorf,
Germany.
Clear cell renal cell carcinomas (RCCs) are characterized by a deletion
of chromosome 3p, which might result in the inactivation of the FHIT
(fragile histidine triad) gene, a putative tumour suppressor gene. To
explore the relevance of FHIT aberrations for tumour progression and
prognosis in clear cell RCCs, FHIT protein expression was analysed in
formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry.
FHIT protein expression was found to be markedly reduced in all RCCs,
when compared with adjacent non-neoplastic tubule epithelia. Although
remaining below the FHIT levels of normal tubule epithelia, a
significant increase of FHIT expression became evident from well (G1) to
poorly (G3) differentiated clear cell RCCs (p=0.0001) and from low (pT1)
to advanced (pT3) tumour stages (p=0.001). The log-rank test
demonstrated a significant inverse correlation (p=0.0074) between FHIT
expression and tumour aggressiveness as indicated by patient survival.
Cox regression analysis revealed that FHIT expression is an independent
prognostic parameter (p=0.0139) in clear cell RCCs. In conclusion, clear
cell RCCs show a marked reduction of FHIT protein expression when
compared with their putative cells of origin. In contrast to other
tumour types, however, loss of FHIT protein expression is significantly
less pronounced in poorly differentiated RCCs or advanced tumour stages.
This versatility of FHIT expression during tumour progression suggests a
role for reversible mechanisms of FHIT inactivation during the
initiation and progression of clear cell RCCs. Copyright 2002 John Wiley
& Sons, Ltd.
27
UI - 11944783
AU - Brandes S B; Smith J B; Longo W E; Virgo K S; Johnson F E
TI -
Renal cell carcinoma in patients with prior spinal cord injury.
SO - J Spinal Cord Med 2001 Winter;24(4):251-6
AD - Division of Urologic Surgery, Washington University School of Medicine,
St Louis, Missouri, USA. brandess@msnotes.wustl.edu
INTRODUCTION: In patients with spinal cord injury (SCI), abdominal
diseases such as renal carcinoma are often diagnosed and treated late in
their course. METHODS: A population-based retrospective review of SCI
patients receiving care for renal cell carcinoma (RCC) in all Department
of Veterans Affairs (DVA) medical centers was conducted for fiscal years
1988 to 1998. RESULTS: Of 96 patients identified, 57 were evaluable and
27 met study criteria. The mean patient age was 59 (range, 41-79 years).
The mean time between SCI and treatment for RCC was 25 years (range,
1-51 years). All patients were men; 22/27 (81%) had 1 or more comorbid
conditions. RCC was an incidental finding on surveillance imaging
studies in 81% (22/27) of the patients. All 27 patients were treated
surgically, 74% (20/27) by radical nephrectomy and 26% (7/27) by partial
nephrectomy. All tumors were renal cell adenocarcinomas. Pathological
staging by the tumor, nodes, and metastasis system was possible in 25;
92% (23/25) of tumors were stage I and 8% (2/25) were stage II.
Postoperative morbidity occurred in 56% (15/27), and death occurred in
7% (2/27). CONCLUSION: In SCI patients in the DVA system, diagnosis of
RCC is usually the result of an incidental finding on surveillance
imaging. Tumors are diagnosed at early stages and partial nephrectomy is
often feasible. Many of the postoperative complications are related to
the SCI, and may be preventable.
28
UI - 11981010
AU - Rabbani F; Herr HW; Almahmeed T; Russo P
TI -
Temporal change in risk of metachronous contralateral renal cell
carcinoma: influence of tumor characteristics and demographic factors.
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