Table of Contents
1
UI - 11275975
AU - Kurokawa T; Oelke M; Mackensen A
TI -
Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes
from renal cell carcinoma patients after stimulation with autologous
dendritic cells loaded with tumor cells.
SO - Int J Cancer 2001 Mar 15;91(6):749-56
AD - Department of Hematology/Oncology, Freiburg University Medical Center,
Freiburg, Germany.
Melanoma and renal cell carcinoma (RCC) are considered to be the most
immunogenic tumors in humans. To generate conditions to induce primary
T-cell responses against RCC and to allow further expansion of
tumor-specific cytotoxic T lymphocytes (CTL) for adoptive transfer,
peripheral blood mononuclear cells from RCC patients were stimulated
with primary autologous tumor cells or monocyte-derived dendritic cells
(DC) loaded with either tumor lysate (TU-LY) or apoptotic tumor cells
(TU-AP). Whereas repetitive stimulation (4x) with tumor cells alone
induced a predominant population of CD3(-) natural killer cells, 4 weeks
of stimulation with tumor-loaded DC favored induction and expansion of
CD4+ T cells (>80%). However, 2 weekly stimulation cycles with
tumor-loaded DC followed by restimulation with autologous irradiated
tumor cells alone were optimal for induction of tumor-specific CTL
responses in vitro. Using these culture conditions a marked increase of
CD4+ T cells was observed during the first 2 weeks of stimulation with
tumor-loaded DC. Subsequent restimulation with autologous tumor cells
alone gave rise to 500-fold expansion of CD8+ T cells. These CD8+ T
cells were shown to exhibit strong major histocompatibility complex
class I-restricted cytotoxic activity against the autologous tumor.
Comparison of TU-LY and TU-AP as a source of tumor antigen for loading
DC did not show any difference in stimulating tumor-specific CTL. Length
pattern analysis of the complementary determining region 3 (CDR3) of the
T-cell receptor Vbeta chain revealed expansion of oligoclonal CTL
populations with outgrowth of 1 or 2 clones after prolonged stimulation
with autologous tumor cells. Our study demonstrated an efficient method
for generating tumor-specific CTL in vitro that may be used to identify
tumor cell antigens or that can be expanded for adoptive T-cell transfer
in tumor immunotherapy. Copyright 2001 Wiley-Liss, Inc.
2
UI - 11248088
AU - Launonen V; Vierimaa O; Kiuru M; Isola J; Roth S; Pukkala E; Sistonen P;
TI -
Herva R; Aaltonen LA
Inherited susceptibility to uterine leiomyomas and renal cell cancer.
SO - Proc Natl Acad Sci U S A 2001 Mar 13;98(6):3387-92
AD - Department of Medical Genetics, Haartman Institute, University of
Helsinki, P. O. Box 21, FIN-00014, Helsinki, Finland.
Herein we report the clinical, histopathological, and molecular features
of a cancer syndrome with predisposition to uterine leiomyomas and
papillary renal cell carcinoma. The studied kindred included 11 family
members with uterine leiomyomas and two with uterine leiomyosarcoma.
Seven individuals had a history of cutaneous nodules, two of which were
confirmed to be cutaneous leiomyomatosis. The four kidney cancer cases
occurred in young (33- to 48-year-old) females and displayed a unique
natural history. All these kidney cancers displayed a distinct papillary
histology and presented as unilateral solitary lesions that had
metastasized at the time of diagnosis. Genetic-marker analysis mapped
the predisposition gene to chromosome 1q. Losses of the normal
chromosome 1q were observed in tumors that had occurred in the kindred,
including a uterine leiomyoma. Moreover, the observed histological
features were used as a tool to diagnose a second kindred displaying the
phenotype. We have shown that predisposition to uterine leiomyomas and
papillary renal cell cancer can be inherited dominantly through the
hereditary leiomyomatosis and renal cell cancer (HLRCC) gene. The HLRCC
gene maps to chromosome 1q and is likely to be a tumor suppressor.
Clinical, histopathological, and molecular tools are now available for
accurate detection and diagnosis of this cancer syndrome.
3
UI - 11332076
AU - Cardillo MR; Lazzereschi D; Gandini O; Di Silverio F; Colletta G
TI -
Transforming growth factor-beta pathway in human renal cell carcinoma
and surrounding normal-appearing renal parenchyma.
SO - Anal Quant Cytol Histol 2001 Apr;23(2):109-17
AD - Departments of Experimental Medicine and Pathology and of Urology,
University La Sapienza, Rome, Italy.
OBJECTIVE: To analyze the role of the transforming growth factor
(TGF)-beta pathway in renal tumors and to verify whether alterations in
TGF-beta 1 pathway expression are associated with the grade of tumor
differentiation and pathologic stage in renal cell carcinomas. STUDY
DESIGN: The expression of TGF-beta 1 and TGF-beta receptors (T beta RI
and T beta RII), SMAD-2 and SMAD-4 was investigated by
immunohistochemistry in normal peritumoral and tumoral tissue from 53
renal cell carcinomas (clear cell type). The gene expression of SMAD-2
and SMAD-4 was also studied by reverse transcription polymerase chain
reaction (RT-PCR) in normal peritumoral and tumoral tissue from 6 of 56
primary tumors. RESULTS: TGF-beta 1, T beta RI and T beta RII
immunoreactivity was more frequent in tumoral than in normal peritumoral
renal tissue (96.22%, 79.25% and 75.41% vs. 88.37%, 69.76% and 62.69%),
whereas SMAD-2 and SMAD-4 immunoreactivity was more frequent in normal
peritumoral than in tumoral tissue (23.25% and 30.23% vs. 15.09% and
7.54%). In tumor areas, immunohistochemical scores were lower for T beta
RII than for T beta RI and TGF-beta 1 and higher than SMAD-4 and SMAD-2
scores. TGF-beta 1, T beta RI, T beta RII and SMAD-4 histologic scores
correlated with neither the histologic grade of malignancy nor TNM
clinical stage, whereas SMAD-2 protein levels were significantly lower
in grade 3 than in grade 1 tumors. In the samples of normal kidney and
carcinoma studied, RT-PCR detected the correct transcripts for SMAD-2
and SMAD-4, indicating that the RNA of the samples analyzed contained
RNA sequences coding for these genes. CONCLUSION: Our data support the
concept that the reduction of T beta RII and SMAD proteins in renal cell
carcinomas is involved in tumor development and suggest an altered
TGF-beta/SMAD signaling pathway in kidney neoplasia.
4
UI - 11394504
AU - Schmidinger M; Steger G; Wenzel C; Locker GJ; Budinsky AC; Brodowicz T;
TI -
Kramer G; Marberger M; Zielinski CC; Austrian Renal Cell Carcinoma Study
Group
Sequential administration of interferon-gamma, GM-CSF, and interleukin-2
in patients with metastatic renal cell carcinoma: results of a phase II
trial.
SO - J Immunother 2001 May-Jun;24(3):257-62
AD - Department of Medicine I, University Hospital, Vienna, Austria.
Various cytokine combinations have been tested for efficacy in the
treatment of metastatic renal cell carcinoma (MRCC). Because several
immunologic synergisms between granulocyte-macrophage
colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been
demonstrated, this phase II trial was conducted on the efficacy and
toxicity of subcutaneous, sequentially administered, interferon-gamma
(IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC
were treated with 100 microg recombinant IFNgamma1b administered thrice
weekly during weeks 1 and 4, followed by 400 microg GM-CSF on 5
consecutive days during weeks 2 and 5. In weeks 3 and 6, patients
received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was
repeated every 8 weeks. Five (10%) of patients experienced an objective
response (complete response [CR]: 2%, partial response [PR]: 8%).
Fourteen (26%) patients had stable disease with a median duration of 19
months (6-47+). The median overall survival was 12 months (range: 0.3-44
months). No toxicity greater than World Health Organization grade II was
observed, with fever (43%) and erythema (43%) being the most frequent
side effects. Compared with other phase II trials with IFN-gamma and
IL-2 alone, the addition of GM-CSF failed to improve response or
survival in patients with MRCC.
5
UI - 11409020
AU - Sullivan M; Frydenberg M
TI -
Nephron-sparing surgery for small incidental renal cell carcinoma.
SO - ANZ J Surg 2001 Jun;71(6):349-53
AD - Department of Urology, Monash Medical Centre, Melbourne, Vic. 3165,
Australia. sullyme@hotmail.com
BACKGROUND: Nephron-sparing surgery is currently an accepted treatment
for renal cell carcinomas in patients with bilateral tumours, solitary
kidneys and when overall renal function is impaired or at risk from
medical disease. Its role in patients with a normal contralateral kidney
remains controversial. METHODS: The authors' experience in 23 patients
undergoing partial nephrectomy for small peripheral lesions between 1995
and 2000 is reported here. RESULTS: Twenty-three patients (13 men and 10
women) with a mean age of 56 years underwent partial nephrectomy. All
but three of these patients had a normal contralateral kidney. Mean
operating time was 141 min with a mean reduction of haemoglobin of 28
g/dL. Three patients required transfusion. Serum creatinine did not
change significantly between preoperative and postoperative values. Two
JJ stents were placed prophylactically during surgery to minimize
urinary leak. There were no intraoperative or early postoperative deaths
and at mean follow up of 16 months there was no evidence of recurrent
tumour in 23 patients. Seventeen per cent of lesions removed were
benign. CONCLUSIONS: Partial nephrectomy for small peripheral lesions is
a safe procedure with low morbidity. No definite recurrences are evident
at an early stage of follow up, although longer review (probably more
than 10 years) will be required to assess cancer-specific survival
following this procedure.
6
UI - 11425235
AU - Lichtenfels R; Ackermann A; Kellner R; Seliger B
TI -
Mapping and expression pattern analysis of key components of the major
histocompatibility complex class I antigen processing and presentation
pathway in a representative human renal cell carcinoma cell line.
SO - Electrophoresis 2001 May;22(9):1801-9
AD - Johannes Gutenberg University, IIIrd Department of Internal Medicine,
Mainz, Germany.
Renal cell carcinoma (RCC) represent approximately 5% of all cancer
deaths. At the time of presentation, over 50% of the patients have
already developed locally advanced or metastatic disease with five-year
survival rates of less than 20%. Although relative resistant to
conventional regimens, RCC are partially susceptible to T cell-based
immunotherapy. To further develop this treatment modality,
two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was
applied for both the mapping of the key components of the major
histocompatibility complex (MHC) class I antigen processing and
presentation machinery (APM) and the characterization of the
constitutive and cytokine-regulated protein expression profiles in a
representative human RCC cell line. The latter aspect is based on the
fact, that the expression level of some of the APM components can be
altered in response to interferon (IFN)-gamma treatment. Total cell
lysates from untreated and IFN-gamma-treated tumor cells were separated
on 2-D PAGE gels using broad range immobilized pH gradient (IPG) strips.
Serial Western blot analyses using sets of APM-specific antibodies were
performed to target the relevant protein spots. Protein verification was
mostly accomplished via peptide mass finger-printing using
matrix-assisted laser desorption/ionization-mass spectrometry
(MALDI-MS). To date, the majority of the APM-related components have
been identified and mapped. In addition, the different protein
expression profiles of untreated and IFN-gamma-treated RCC cells are
under investigation.
7
UI - 11432624
AU - Tate J; Olencki T; Finke J; Kottke-Marchant K; Rybicki LA; Bukowski RM
TI -
Phase I trial of simultaneously administered GM-CSF and IL-6 in patients
with renal-cell carcinoma: clinical and laboratory effects.
SO - Ann Oncol 2001 May;12(5):655-9
AD - Department of Hematology and Medical Oncology, The Cleveland Clinic
Foundation, Ohio, USA.
BACKGROUND: Metastatic renal-cell carcinoma is a neoplasm that is
minimally responsive to cytotoxic chemotherapy. Tumor regression
following therapy with cytokines such as interferon alpha and or
interleukin-2 is seen in selected subsets of patients. Investigations
with other immunomodulatory cytokines, such as GM-CSF and IL-6 are
therefore of interest. PATIENTS AND METHODS: A phase I trial of
concomitantly administered granulocyte macrophage-colony stimulating
factor (3.0 mcg/kg/day s.c. d1-14) and escalating doses of interleukin-6
(1.0, 5.0 or 10.0 microg/kg/day d1-14) was conducted in patients with
metastatic renal-cell carcinoma to explore the toxicity of the
combination and its hematologic effects. RESULTS: The most common side
effects seen were fever, fatigue and arthralgias. Dose limiting toxicity
included thrombocytosis and hyperbilirubinemia in patients receiving 10
microg/kg/day of IL-6. The hematologic effects of IL-6 and GM-CSF
included leukocytoses and thrombocytosis, with increases in peripheral
blood progenitors (BFU-E, CFU-GM, and CFU-GEMM). Evidence of platelet
activation demonstrated by increased platelet expression of CD62 was
found. No clinical responses were observed. CONCLUSIONS: The combination
of IL-6 and GM-CSF has pleotropic hematologic effects. Further studies
with this combination for the treatment of renal-cell carcinoma are not
recommended.
8
UI - 11444733
AU - Johnson PT; Nazarian LN; Feld RI; Needleman L; Lev-Toaff AS; Segal SR;
TI -
Halpern EJ
Sonographically guided renal mass biopsy: indications and efficacy.
SO - J Ultrasound Med 2001 Jul;20(7):749-53; quiz 755
AD - Department of Radiology, Thomas Jefferson University Hospital,
Philadelphia, Pennsylvania, USA.
PURPOSE: To review the clinical indications, pathologic results, and
success rate of all our sonographically guided solid renal mass biopsies
over a 5-year period. METHODS: Between 1993 and 1998, 44 consecutive
patients underwent sonographically guided percutaneous biopsy of a solid
renal mass. Indications included prior history of nonrenal malignancy,
metastatic disease of unknown primary origin, previous contralateral
nephrectomy for a renal cell neoplasm, a renal transplant mass,
suspected renal lymphoma, history of tuberous sclerosis, and poor
surgical candidacy. Aspiration biopsies were initially performed with
22- to 18-gauge spinal needles. If the initial cytologic evaluation
findings were nondiagnostic, core biopsies were then performed with 20-
to 18-gauge core biopsy guns. Dictated sonographic reports of the
biopsies were reviewed to determine the following: indication for
biopsy, location and size of the renal mass, needle gauge and type,
number of needle passes, and complications. Final cytologic and surgical
pathologic records were reviewed. RESULTS: Thirty-six (82%) of the 44
biopsy specimens were diagnostic. Aspirated smears were diagnostic in 24
(67%) of these cases, with the diagnosis made on the basis of cell block
alone in an additional 2 (6%). A definitive diagnosis came from core
biopsy alone in 10 cases (28%). The 18-gauge core needle yielded
diagnostic results more reliably than the 20-gauge core needle, and a
significant correlation was seen between core biopsy needle size and the
rate of diagnostic core samples (P = .017). Pathologic diagnoses
included renal cell carcinoma (n = 18), lymphoma (n = 4), oncocytic
neoplasm (n = 4), transitional cell carcinoma (n = 2), angiomyolipoma (n
= 1), papillary cortical neoplasm (n = 1), and metastatic carcinoma (n =
6). Complications were seen in 4 (9%) of 44 cases; all were treated
conservatively. CONCLUSIONS: For specific clinical indications,
sonographically guided fine-needle aspiration and core biopsy of a solid
renal mass can be performed safely. In many cases, a definitive
diagnosis can be made on the basis of fine-needle aspiration alone.
However, diagnosis may ultimately require core biopsy, for which
18-gauge core needles would be more reliably diagnostic than 20-gauge
needles.
9
UI - 11455829
AU - Congregado Ruiz B; Medina Lopez RA; Sanchez Gomez E; Morales Lopez A;
TI -
Pascual del Pobil JL
[Incidental diagnosis of renal carcinoma. Does it imply a better
prognosis?]
SO - Actas Urol Esp 2001 Apr;25(4):278-82
AD - Unidad de Uro-oncologia, Servicio de Urologia, Hospital Universitario
Virgen de Rocio, Sevilla.
OBJECTIVE: We present 267 patients undergoing surgery for renal
carcinoma, comparing the incidental tumour and symptomatic tumour with
different parameters and evaluating the prognostic significance of the
incidental diagnosis. MATERIAL AND METHODS: Of the 267 patients, 110
(41.2%) were diagnosed incidentally. The different variables analysed
were: age, sex, tumour size, if unilateral or bilateral, histological
type, stage, degree of cellular differentiation and survival. The mean
follow-up period was of 43.32 mos in the symptomatic patients and 41.85
mos in the patients diagnosed incidentally. The data obtained was
analysed with the SPSS statistic pack. RESULTS: No significant
difference was detected between both groups in regards to age, sex, if
unilateral or bilateral and histological type. Comparing tumour size, a
statistic difference was observed with slices at 6 cm. When analysing
the stage and degree of cellular differentiation, a significant
difference is found with tumours diagnosed incidentally presenting
better differentiation and a lower stage at the moment of diagnosis.
Survival after 5 yrs was of 65.7% for symptomatic patients in comparison
to 81.7% for the incidental group, which implies high statistical
signification (log rank = 0.0018). CONCLUSIONS: In our series no
significant differences were detected between incidental and symptomatic
tumours when comparing age, sex, anatomic side and histological type.
Significant differences were indeed detected in relation to size, degree
of cellular differentiation, tumour stage and survival.
10
UI - 11471899
AU - Lissoni P; Rovelli F; Vellani D; Malugani F; Bucovec R; Chapovalenko L;
TI -
Fumagalli E; Gardani G
Stimulation of IL-18 secretion by IL-2 in patients with advanced cancer.
SO - Int J Biol Markers 2001 Apr-Jun;16(2):146-7
11
UI - 11482081
AU - Zlomaniec J; Lech B; Feldo D; Zlomaniec G; Jedrzejewski G; Mosiewicz J;
TI -
Piasecka K
Diagnostic difficulties in cystic renal tumors.
SO - Ann Univ Mariae Curie Sklodowska [Med] 2000;55():245-52
AD - II Zaklad Radiologii Akademii Medycznej w Lublinie.
12
UI - 11484974
AU - Casali M; Marcellini M; Casali A; Giuntini T; Galante E; Ferrone C
TI -
Gemcitabine in pre-treated advanced renal carcinoma: a feasibility
study.
SO - J Exp Clin Cancer Res 2001 Jun;20(2):195-8
AD - S.C. Oncologia medica C, Istituto Regina Elena, Roma, Italy.
Eigtheen patients affected by metastatic renal cell carcinoma, 16 which
were assesable, were treated with 1 g/m2 of Gemcitabine (GCB) on days 1,
8 and 15 of a 28-day treatment cycle up to a maximun of ten cycles. All
patients in neoplastic progression were treated with chemo- and
immunotherapy (5 FU, IL-2, IFN alpha d 13-cis-retinoic acid.) Out of the
16 assessable patients, 5/16 (31%) showed overall response (ICR, 4 PR),
5 (31%) stable disease (SD) and 6 (38%) progression of disease (PD).
Toxicity was limited to WHO grades I only, primarily hematological.
13
UI - 11517826
AU - Lancini V; Liatsikos EN; Bernardo NO; Dinlenc CZ; Kapoor R; Smith AD
TI -
[Endourologic treatment of transitional cell carcinoma of the upper
urinary tract]
SO - Minerva Urol Nefrol 2000 Mar;52(1):17-28
AD - Department of Urology, Long Island Jewish Medical Center, Albert
Einstein College of Medicine, 270-05 76th Avenue-New Hyde Park, NY
11042, USA.
Nephrourete-rectomy with excision of a bladder cuff has been the
standard treatment of the upper urinary tract transitional cell
carcinoma. The very indolent behavior (GI, II, Ta, T1) of more than 50%
and up to 82% of the upper urinary tract tumors treated with
nephroureterectomy in different series in conjunction with the advent of
sophisticated endourological techniques have permitted in certain cases
alternative treatments using a conservative approach with either
ureteropyeloscopy or percutaneous access. Ureteroscopy is reserved for
ureteral tumors and small, simple tumors of the renal pelvis (< 1.5 cm)
while large or multiple tumors of the renal pelvis are approached in a
percutaneous way. During 14 years 64 patients with transitional cell
carcinoma of the upper urinary tract were treated percutaneously at our
department at Long Island Jewish Medical Center, 15 (23.5%) with grade
I, 26 (40.6%) with grade II and 23 (35.9%) with grade III and IV. After
a mean follow-up of 51 months, percutaneously treated patients had a
tumor specific survival of 85.6%, being 100% for GI tumors, 96.1% for
GII and 60.8% for GIII. Recurrence of grade I tumors were observed in
20%, 26.9% for grade II and 56.5% for Grade III. In conclusion, with a
rigorous follow-up transitional cell carcinoma of the upper tract with
low and moderate grades (GI, GII, Ta, T1) can be treated endorologically
even in the presence of a normal contralateral kidney with low morbility
and a long term efficiency comparable to a nephroureterectomy. An
elective endorologic management for GIII tumors is not recommended.
Endoscopic conservative surgery can be offered when the criteria of good
prognosis are found for Ta (such as absence of carcinoma in situ,
presence of diploidy, low p53 expression and a single tumor) and in the
cases of a solitary kidney or chronic renal insufficiency or for poor
surgical candidates for T1. Patients with stage T2-T3 should be offered
a nephroureterectomy.
14
UI - 11528247
AU - Elias L; Hunt WC
TI -
A literature analysis of prognostic factors for response and quality of
response of patients with renal cell carcinoma to interleukin-2-based
therapy.
SO - Oncology 2001;61(2):91-101
AD - Department of Internal Medicine, Division of Hematology and Medical
Oncology, University of New Mexico School of Medicine and Cancer
Research and Treatment Center, Albuquerque, NM, USA.
Laurence_Elias@matx.com
OBJECTIVE: To characterize prognostic factors for response of advanced
renal cell carcinoma to interleukin-2-based regimens. PATIENTS AND
METHODS: Data compiled from 80 published series were examined for
associations between patient characteristics and outcomes. RESULTS:
Response rates were highest in trials utilizing interleukin-2
combinations. Longer median survivals were associated with high
percentages of patients with nephrectomy, good performance status, with
publication year, response rates, and inversely with median ages.
Associations of performance status and prior nephrectomy with response
rates were detected in trials with individual patient details. The
response rate was higher for patients older than the median age of
patients entering each trial, and also higher for males. Among
responders, attainment of complete response was associated with fewer
sites of involvement. Pooled response duration of patients reported to
have complete responses exhibited durability, but no correlation with
prognostic factors. Selection factors may have influenced apparent
differences between types of regimens. We confirm the potential for
durable remissions from interleukin-2-based regimens. Copyright 2001 S.
Karger AG, Basel
15
UI - 11547111
AU - Koyle MA; Hatch DA; Furness PD 3rd; Lovell MA; Odom LF; Kurzrock EA
TI -
Long-term urological complications in survivors younger than 15 months
of advanced stage abdominal neuroblastoma.
SO - J Urol 2001 Oct;166(4):1455-8
AD - Department of Pediatric Urology, Children's Hospital and University of
Colorado School of Medicine, Denver, Colorado, USA.
PURPOSE: We evaluated the long-term urological complications in
survivors of infant advanced stage abdominal neuroblastoma. MATERIALS
AND METHODS: The records of patients who presented during an 8-year
period with surgical problems related to the kidney and who had survived
advanced stage (IV and IV-S) neuroblastoma were reviewed. RESULTS: Of 7
patients identified 3 had complications of obstruction from
retroperitoneal fibrosis and 4 had renal cell carcinoma. In the renal
cell carcinoma group 3 patients had synchronous, multifocal, bilateral
tumors and 1 had a tumor in a solitary kidney. Pathological examination
of renal cell carcinoma revealed oncocytoidy with solid and papillary
patterns. One patient underwent bilateral nephrectomy but in the
remaining 3 renal preservation surgery was performed. All 7 patients
have no progression of secondary complications 2 to 8 years after
initial presentation. CONCLUSIONS: Survivors of advanced stage abdominal
neuroblastoma may be predisposed to long-term urological complications
well after initial diagnosis. Because of the risk of renal damage from
obstruction secondary to retroperitoneal fibrosis, and the propensity to
have renal cell carcinoma, close long-term followup using abdominal
imaging is recommended.
16
UI - 11549480
AU - Carvalhal EF; Gill IS; Meraney AM; Desai MM; Schweizer DK; Sung GT
TI -
Laparoscopic renal cryoablation: impact on renal function and blood
pressure.
SO - Urology 2001 Sep;58(3):357-61
AD - Section of Laparoscopic and Minimally Invasive Surgery, Urological
Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
OBJECTIVES: To evaluate the renal function and blood pressure outcomes
after laparoscopic renal cryotherapy. Laparoscopic renal cryoablation is
a developmental minimally invasive modality for the treatment of renal
neoplasms. After cryotherapy, a segment of renal parenchyma is rendered
ischemic/necrotic and left in situ. It is currently unknown whether this
may trigger renin overproduction and thus renin-mediated hypertension.
METHODS: Data are presented for 22 of 56 treated patients, each of whom
completed a minimum follow-up of 6 months. The data were obtained from
patient charts, phone interviews, and/or questionnaires. These results
were statistically compared over time by paired t tests. RESULTS: The
mean follow-up was 20.6 months. No significant differences were found
between the preoperative and most recent postoperative serum creatinine
(sCr) levels (1.13 and 0.91 mg/dL, respectively), systolic and diastolic
blood pressure values (135.6 versus 131.2 mm Hg and 78 versus 72.7 mm
Hg, respectively), or in the estimated creatinine clearance (P <0.05).
The number or dose of antihypertensive medications did not change during
the follow-up period for any patient. In 3 patients with a solitary
kidney, the blood pressure and sCr values remained unchanged (mean
preoperative sCr 1.43 mg/dL and mean postoperative sCr after a minimum
of 6 months 1.33 mg/dL). CONCLUSIONS: Laparoscopic renal cryoablation
did not have a deleterious impact on renal function or blood pressure
during a mean follow-up of 20.6 months.
17
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.
18
UI - 11558060
AU - Rickes S; Flath B; Unkrodt K; Ocran K; Neye H; Lochs H; Wermke W
TI -
[Pancreatic metastases of renal cell carcinomas - evaluation of the
contrast behavior at echo-enhanced power-Doppler sonography in
comparison to primary pancreatic tumors]
SO - Z Gastroenterol 2001 Aug;39(8):571-8
AD - Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und
Endokrinologie, Berlin, Germany. steffen.rickes@charite.de
BACKGROUND: Renal cell carcinomas are the most common primary tumors
leading to pancreatic metastases. The differentiation of metastases from
primary pancreatic tumors is important for the prognosis. Echo-enhanced
power-Doppler sonography may be used for the differential diagnosis of
tumors. In this study, the contrast behavior of metastases of renal cell
carcinomas was evaluated in comparison to primary pancreatic
tumors.PATIENTS AND METHODS: Each 5 patients with pancreatic metastases
of a renal cell carcinoma, a ductal carcinoma, a neuroendocrine tumor
and a pancreatitis-associated mass were investigated by B-mode
sonography, fundamental and echo-enhanced power-Doppler
sonography.RESULTS: Similar to neuroendocrine tumors, metastases of
renal cell carcinomas were found to be hypervascularized. In contrast,
ductal carcinomas are hypovascularized compared to the surrounding
tissue. Tumors associated with pancreatitis show different
vascularization pattern depending on inflammation and
necrosis.CONCLUSIONS: Metastases of renal cell carcinomas and ductal
carcinomas show different vascularization pattern at echo-enhanced
power-Doppler sonography. Renal cell metastases and neuroendocrine
tumors have similar contrast behaviors, therefore, clinical symptoms
should be referred for their differentiation. However, histology is the
standard of reference for the differential diagnosis of pancreatic
tumors.
19
UI - 11568972
AU - Nojima D; Nakajima K; Li LC; Franks J; Ribeiro-Filho L; Ishii N; Dahiya
TI -
R
CpG methylation of promoter region inactivates E-cadherin gene in renal
cell carcinoma.
SO - Mol Carcinog 2001 Sep;32(1):19-27
AD - Department of Urology, Veterans Affairs Medical Center and University of
California San Francisco, 94121, USA.
CpG methylation in the promoter region has been shown to be important in
the regulation of genes implicated in malignant transformation. The
present study was designed to test the hypothesis that CpG methylation
of the promoter region of the E-cadherin gene may inactivate its
expression in renal cell carcinoma. To test this hypothesis, five kidney
cancer cell lines and 34 microdissected renal cell carcinoma samples
were analyzed for gene and protein expression by reverse
transcription-polymerase chain reaction and immunohistochemistry,
respectively. CpG methylation in the promoter regions of the E-cadherin
gene was analyzed by the sodium bisulfite genome sequencing technique.
Our results show that all normal renal tissue expressed the E-cadherin
gene and protein. Of the renal cancer tissues analyzed, 67% (23 of 34)
lacked E-cadherin expression, with an associated increase in
methylation, compared with normal tissue. E-cadherin gene promoter was
methylated in all renal cancer cell lines and was accompanied by a loss
of E-cadherin gene and protein expression. The treatment of renal cancer
cell lines with the demethylating agent 5-aza-2'-deoxycytidine restored
E-cadherin mRNA expression in all renal cancer cell lines. This is the
first report that shows inactivation of the E-cadherin gene and protein
in renal cell carcinoma through CpG hypermethylation in the promoter
region of this gene. The results of these experiments may contribute to
an understanding of the role of E-cadherin inactivation in renal cell
carcinoma. Copyright 2001 Wiley-Liss, Inc.
20
UI - 11593561
AU - Zhuang L; Zhang Z; Guo Y
TI -
Aberrant expression of growth factor Wnt-5A in six urinary malignant
cell lines.
SO - Chin Med J (Engl) 1999 Mar;112(3):251-5
AD - Department of Urology, First Hospital, Beijing Medical University,
Institute of Urology, Beijing Medical University, Beijing 100034, China.
OBJECTIVE: To investigate the expression of growth factor Wnt-5A in
urinary tumor cell lines. METHODS: By semi-quantitative RT-PCR (reverse
transcriptase polymerase chain reaction), the expression of Wnt-5A in
six urinary malignant cell lines, one primary cultured renal fibroblast
and one case of normal human renal tissue was detected using Gel Doc
1000 computer controlled molecular analysis system. RESULTS: The
expression of Wnt-5A in-urinary tumor cell lines was much higher than
that in primary cultured renal fibroblasts (PRF) and normal human renal
tissue (NRT). The levels of Wnt-5A mRNA were different between six
malignant cell lines. CONCLUSION: The overexpression of growth factor
Wnt-5A has a potential effect on the oncogenesis of urinary
malignancies.
21
UI - 11585973
AU - Twelves C
TI -
Vision of the future: capecitabine.
SO - Oncologist 2001;6 Suppl 4():35-9
AD - Cancer Research Campaign Department of Medical Oncology, University of
Glasgow, and Beatson Oncology Centre, Glasgow, United Kingdom.
c.twelves@beatson.gla.ac.uk
Capecitabine is a thymidine phosphorylase (TP)-activated oral
fluoropyrimidine, rationally designed to generate 5-fluorouracil (5-FU)
preferentially within tumors. This tumor selectivity is achieved through
exploitation of the significantly higher activity of TP in tumor
compared with healthy tissue. The high single-agent activity of
capecitabine in breast and colorectal cancer suggests that capecitabine
may have a role in the treatment of other tumor types that are sensitive
to 5-FU, such as pancreatic cancer. Tumor types known to have a high
level of TP activity, such as renal cancer, are especially attractive
targets for capecitabine therapy. Capecitabine has potential as
monotherapy in these tumor types, or as a combination partner for other
cytotoxic agents with different mechanisms of action and little overlap
of key toxicities. In particular, some cytotoxic drugs, such as the
taxanes and cyclophosphamide, are known to upregulate TP activity in
tumor tissue, offering the potential for synergistic action. The
combination of capecitabine and docetaxel has demonstrated significant
activity in women with anthracycline-pretreated breast cancer, and is
the only cytotoxic combination to significantly increase survival
compared with standard therapy in this setting. In addition,
capecitabine as monotherapy or in combination with other cytotoxic
agents has shown encouraging activity in pancreatic, ovarian, and renal
cell cancers. This article discusses recent data from clinical trials
investigating capecitabine in a range of tumor types, highlighting the
potential future role of capecitabine as an alternative to traditional
i.v. chemotherapy.
22
UI - 11585680
AU - Capuron L; Ravaud A; Gualde N; Bosmans E; Dantzer R; Maes M; Neveu PJ
TI -
Association between immune activation and early depressive symptoms in
cancer patients treated with interleukin-2-based therapy.
SO - Psychoneuroendocrinology 2001 Nov;26(8):797-808
AD - INSERM U.394, Neurobiologie Integrative, Institut Francois Magendie,
33077, Bordeaux Cedex, France. lcapuro@emory.edu
The relationship between immune activation and the development of early
depressive symptoms were studied in 33 cancer patients undergoing
cytokine therapy. Patients were treated either with subcutaneous IL-2
administered alone (n=13) or in association with IFN-alpha (n=5), or
with IFN-alpha alone administered subcutaneously at low doses (n=5) or
intravenously at high doses (n=10). The intensity of depressive symptoms
was asses
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