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PubMedDate not supplied

Influence of tumor site on the therapy of murine kidney cancer.

OBJECTIVE: The purpose of this study was to evaluate the influence of tumor site on the therapy of an experimental murine kidney cancer model, Renca. METHODS: Equal number of tumor cells were injected subcutaneously, intraperitoneally, sub-renal capsule, and intravenously to induce tumors. The animals were then assessed for growth of the primary tumor, metastases and survival. Immunohistochemistry and flow cytometry was performed to identify the phenotype of infiltrating lymphocytes. Tumor bearing animals were treated with high dose interleukin-2 or whole body radiation, and response of the primary tumors as well as the metastases was assessed. RESULTS: Renca tumors grew well regardless of the methods of induction. Spontaneous metastasis could be best induced in the sub-renal capsule model. More consistent numbers of pulmonary metastases were obtained by intravenous injection of the tumor cells. Immunotherapy was able to reduce the size of the primary tumor as well as the number of metastasis. Whole body radiation caused some reduction in the primary tumor but did not have a major effect in reducing metastasis. CONCLUSIONS: The Renca model is a suitable animal model to study the response to different therapeutic interventions. The site of the tumor growth is not a significant variable in the response to treatment.

Adenocarcinoma↗
PubMed1992

Risk factors for kidney cancer in New South Wales, Australia. II. Urologic disease, hypertension, obesity, and hormonal factors.

In a population-based case-control study of kidney cancer in New South Wales, Australia, data from structured interviews with 489 cases of renal cell cancer (RCC) and 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls, confirmed the link between obesity and RCC. In addition, regular consumption of 'diet' pills independently increased the risk for this cancer. A diagnosis of hypertension at least two years before interview raised the risk for RCC, and regular use of beta-blockers, a class of antihypertensive drug, independently increased the risk for RCC and CaRP (risk ratio = 1.5-1.8). No independent effect was found for use of diuretics. Additional information provided by this study includes increased risks associated with kidney injury (RCC, CaRP)--possibly attributed to recall bias--and kidney infection (CaRP), as well as a nonsignificantly raised risk linked with kidney stones (RCC, CaRP) and a significantly reduced risk for RCC in persons giving a history of lower urinary tract infection. No significant association of RCC was found with hormonal factors (age at menarche or menopause; child-bearing; regular use of oral contraceptives or estrogens; hysterectomy or oophorectomy).

Adult↗
PubMed2002

Laparoscopic radical nephrectomy for advanced kidney cancer.

The management of advanced renal cell carcinoma (RCC) continues to evolve. With the advent of laparoscopic radical nephrectomy (LRN), minimally invasive approaches to kidney cancer have developed. Laparoscopic resection of locally advanced RCC yields a similar cancer-control rate with the advantage of decreased morbidity. Although cytoreductive LRN is a technically challenging procedure, it may be completed safely in selected patients. Further prospective study of the role of LRN for advanced RCC is warranted.

Carcinoma, Renal Cell↗
PubMed2006

Radiofrequency ablation in the treatment of kidney cancer.

(1) The standard approach for the treatment of kidney (renal) cancer is radical or partial nephrectomy (removal of the kidney). (2) Radiofrequency ablation (RFA), a less invasive approach, is an option for the treatment of small tumours, and in cases where surgery is contraindicated. (3) Its safety and efficacy compare favourably with those of other approaches. (4) The persistence of residual tumour is a disadvantage of earlier versions of the technology. The use of more powerful radiofrequency (RF) generators may reduce such persistence, but definitive evidence is unavailable. (5) Experience with this application of the technology is limited. Longer follow-up of patients is required to provide an adequate comparison with nephrectomy.

Canada↗
PubMed1991

Effects of high-energy shock waves combined with biological response modifiers in different human kidney cancer xenografts.

We have studied the effects of high-energy shock waves (HESW) alone or in combination with biological response modifiers on the growth of five human kidney cancer xenografts in mice. Exposure of the tumors to three sessions of 800 shock waves every 48 hours with 18.4 kV, 37.5 MPa, on the commercially available Lithostar resulted in a temporary growth delay. The sensitivity for HESW was related to the doubling time of the tumor. Several days after stopping the HESW administration, the tumors regained their original growth potential with the same doubling time. The systemic application of Tumor Necrosis Factor-alpha (TNF-alpha, 500 ng/g body weight, 5 times/week) and/or Interferon-alpha (IFN-alpha, 5.0 ng/g body weight, 3 times/week) subcutaneously around the tumor also had a limited effect on the growth of these established tumors (60-80 mm3). The combination of HESW with TNF-alpha and IFN-alpha resulted in an almost complete cessation of tumor growth in the NU-1 human kidney xenograft and had an additive antitumor effect in the NU-3. Synergism was also seen in the NU-1 and NU-3 with the combination of HESW and TNF-alpha, while the combination with IFN-alpha had only a limited effect on tumor growth. So TNF-alpha was the active agent, that enhanced the antiproliferative effects of shock waves. In the NC-65 tumor (same doubling time as the NU-1 and NU-3, but less well vascularized), the antiproliferative effect of HESW was not potentiated by TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of high-energy shock waves combined with biological response modifiers or Adriamycin on a human kidney cancer xenograft.

We have studied the effect of high-energy shock waves (HESW) alone or in combination with biological response modifiers (BRMs) or Adriamycin on the growth of the NU-1 human kidney cancer xenograft. When HESW are administered repeatedly (four sessions of 800 shock waves on days 0, 2, 4 and 6) a prolonged delay in tumor growth was found compared with that following a single administration. This effect was temporary, and several days after stopping the HESW administration the tumor regained its original growth potential (same doubling time). Tumor growth was suppressed for a longer period by the combination of 4 sessions of HESW and a single administration of Adriamycin, 5 mg/kg. Combination of HESW treatment with interferon alpha (5.0 ng/g body weight, three times/week) and tumor necrosis factor alpha (500 ng/g body weight, 5 days/week) s.c. around the tumor resulted in a complete cessation of tumor growth. While Adriamycin had an additive effect on HESW treatment, the combination with BRMs was highly synergistic.

Animals↗
PubMed2006

Organ-preserving endoscopic kidney cancer resection.

OBJECTIVE: Recently, minimally invasive therapies for renal cell carcinoma have been devised to minimise operative morbidity yet achieve comparable oncologic and functional outcomes. This video summary of laparoscopic transperitoneal organ-preserving kidney cancer resection shows the procedure from the surgeon's view. METHODS: The video and photos show the main steps of the procedure. The results of 40 transperitoneal and retroperitoneal procedures performed during 2001-2005 are discussed. Preoperative preparation includes abdominal computed tomography and ureteral catheterisation. Tumour margins were determined by laparoscopic renal ultrasonography. Vessel control was done by en bloc clamping or solitary clamping of the artery. For optimal macroscopic evaluation of the resection margins, tumour excision was solely done with cold Endoshears followed by pelvicaliceal suture repair and parenchymal closure over surgical bolsters with a biologic haemostatic agent. RESULTS: In 40 cases, we converted to the open procedure only once. The average patients age was 53 yr and mean tumour size was 26 mm. No patient showed positive surgical margins. The mean warm ischemia time was 21 min. Final histopathology revealed renal clear cell carcinoma as the major cell type followed by papillary renal carcinoma. Two patients required blood transfusion. Estimated mean blood loss was 270 ml. Median time of hospitalisation was 6 d. CONCLUSION: Endoscopic partial nephrectomy can be performed by experienced surgeons in selected patients. Tumour location and size and the surgeons' experience and preference are the main parameters to make the decision of the type of access.

Endoscopy↗
PubMed1996

[Arteriovenous fistula with cardiac insufficiency disclosing kidney cancer].

A 66 year-old woman free of any coronary and valvular heart disease presented to our hospital with acute and severe congestive heart failure associated with increased blood flow-angiography showed an intraparenchymatous arteriovenous fistula of the left kidney and a kidney cancer. The patient was discharged after nephrectomy and complete heart recovery as assessed from the normality of the hemodynamic exploration of the right ventricle.

Aged↗
PubMed1993

A 39-year follow-up of the U.K. oil refinery and distribution center studies: results for kidney cancer and leukemia.

This paper presents briefly some of the principal results of a mortality analysis of a cohort of workers employed for at least 1 year between 1950 and 1975 at eight oil refineries and approximately 750 distribution centers in the U.K., together with detailed results for kidney cancer and leukemia. Over 99% of the workers were successfully traced. Their mortality was compared with that of all males in the national population. The mortality from all causes of death is lower than that of the comparison population in both studies, and reduced mortality is also found for many of the major nonmalignant causes of death. In the refinery study, some increased mortality patterns are found for diseases of the arteries, and no healthy worker effect is found in the distribution center study for ischemic heart disease. Mortality from all neoplasms is lower than expected overall in both studies, largely due to a deficit of deaths from malignant neoplasm of the lung. Mortality from malignant neoplasm of the kidney is increased overall in the distribution center study, and in drivers in particular. The mortality from this disease increases with increased time since first exposure. The observed deaths from leukemia are slightly less than expected in the refinery study and slightly more than expected in the distribution center study. One refinery shows increased mortality due to in myeloid leukemia, and mortality is increased among refinery operators. Mortality is also raised in distribution center drivers, particularly for myeloid leukemias, including acute myeloid leukemia.

Cause of Death↗
PubMed1987

Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene.

The cloning of the cDNA for the mdr1 gene, whose expression is associated with the development of multidrug-resistance in cultured cells, has made it possible to explore the mechanism of multidrug resistance in human tumors. We have found that normal human kidney, six of eight adenocarcinomas of the kidney, and four cell lines derived from kidney adenocarcinomas express high levels of mdr1 mRNA. Two criteria suggest that primary multidrug resistance in human adenocarcinomas of the kidney results, at least in part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated in four unselected kidney adenocarcinoma cell lines that show a multidrug-resistant phenotype; and (2) multidrug resistance in these kidney cancer cell lines is reversed by verapamil and quinidine, agents known to reverse mdr1-associated drug resistance in cell lines selected for multidrug resistance in vitro. These results suggest that appropriate pharmacological intervention to reverse multidrug resistance might make adenocarcinomas of the kidney more sensitive to chemotherapy with agents such as Adriamycin (Adria Laboratories, Columbus, OH) and the vinca alkaloids.

Cell Line↗
PubMed2003

Racial disparity in incidence patterns and outcome of kidney cancer.

OBJECTIVES: To identify the subgroups that primarily contribute to the greater incidence and mortality of renal cancer in black Americans compared with white Americans. METHODS: We analyzed age, stage, and race-related differences in the incidence and survival among patients with renal cancer using the national Surveillance, Epidemiology, and End Results (SEER) registry database. White and black patients with renal cell carcinoma who were older than 19 years of age and had been diagnosed between 1975 and 1998 were included. Incidence trends were analyzed by joinpoint regression with the statistical significance level at P <0.05. The Cox proportional hazards model was used to determine the overall survival of patients with renal cell carcinoma by race (white versus black), age (20 to 59 versus 60+ years), and stage (local versus regional/distant). RESULTS: Localized disease predominantly accounted for the rise in incidence. Both black age groups with localized disease had a greater estimated annual percentage of incidence increase (4.46% for 20 to 59 years and 4.35% for 60+ years) compared with their white counterparts (2.87% and 3.06%, respectively). The magnitude of survival difference was largest between black versus white patients younger than 60 years of age who had local stage disease, with a median survival time of 190 and 259 months, respectively (P <0.0001). CONCLUSIONS: Young black patients with localized renal cancer appear to have had a greater rise in incidence and a poorer outcome than white patients of the same age and disease stage. Additional investigation is warranted to define the role of these race, stage, and age-related disparities in the etiology, prognosis, treatment, and follow-up of kidney cancer.

Adult↗
PubMed2006

Kidney cancer therapy: new perspectives and avenues.

Immunotherapy with interleukin-2 and interferon-alpha has been the only viable option in metastatic renal cell cancer for almost two decades. In the last several years, significant advances in the understanding of the underlying biological and molecular mechanisms of renal cell carcinoma, particularly the role of tumour angiogenesis, have led to the identification of rational therapeutic targets and permitted the design of molecularly targeted therapeutics. At present, new compounds targeting specific signalling pathways are available and have successfully passed clinical testing. The use of small molecules, such as multitargeted tyrosine kinase inhibitors, the mTOR inhibitors and monoclonal antibodies, is dramatically changing the existing concepts of systemic treatment for metastatic kidney cancer.

Antineoplastic Agents↗
PubMed2002

Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1 is impaired by a somatic mutation found in kidney cancer.

Oxidative damage to mitochondrial DNA (mtDNA) has been implicated as a contributing factor to the origin of many pathological processes. Among the major DNA lesions generated by oxidative stress, 8-oxoguanine (8-oxoG) has a strong mutagenic potential. The main pathway for the repair of this lesion is the base excision repair (BER) initiated by the OGG1 DNA glycosylase. In human cells alternative splicing of the hOGG1 transcript yields two forms of the protein, alpha and beta, that are localised in the nucleus and the mitochondria, respectively. We describe here a hOGG1 somatic mutation, found in a kidney cancer, that modifies the intracellular localisation of beta-hOGG1. The glycine 12 to glutamic acid substitution does not affect the enzymatic activity of the enzyme but lies in what was predicted to be a mitochondrial targeting sequence (MTS). Immunocytochemical localisation experiments show that the G12E mutant protein has diffuse cytoplasmic distribution instead of the mitochondrial localisation found for the wild-type, providing an example of a single amino acid substitution capable of disrupting a MTS. These results imply that these cancer cells are deficient in their mitochondrial 8-oxoG DNA repair activity.

Cell Nucleus↗
PubMedDate not supplied

The kidney, cancer, and the eye: current concepts.

Herein, we review the associations between the kidney, renal cancers, and the eye. Renal cancers have been reported to metastasize to the eye and the orbit. As these tumors can be confused with other amelanotic or vascular tumors, a high index of suspicion is required for early detection and management of the primary tumor. We discuss the physiology of metastases, clinical features and management of metastatic disease. A variety of ocular anomalies have been associated with renal disease. Wilms tumor, a renal tumor of childhood, can present with aniridia, which may be the first clue leading to the diagnosis of the primary tumor. Paraneoplastic syndromes are common manifestations of renal cancers and can present as retinopathies and neuro-ophthalmic disorders. Multiple cancer syndromes involve both the eye and the kidney. For example, the diagnosis of von Hippel retinal tumors can lead to a systemic evaluation and discovery of associated visceral tumors. The prognosis, screening, and counseling of such patients is discussed. Newer systemic treatments available for renal tumors, such as interferon alfa, may lead to ocular side effects including retinopathy. These patients require periodic ophthalmic examinations. This review demonstrates the essential role of the ophthalmologist, for early diagnosis and treatment that can help reduce the morbidity and mortality associated with kidney tumors and renal-associated disease.

Carcinoma, Renal Cell↗
PubMed1997

Health related quality of life outcomes in patients treated for metastatic kidney cancer: a pilot study.

PURPOSE: We assessed health related quality of life in patients with advanced renal cell carcinoma treated with nephrectomy and tumor infiltrating lymphocyte therapy in combination with interleukin-2. MATERIALS AND METHODS: A total of 20 patients with advanced renal cell carcinoma who underwent nephrectomy and combination immunotherapy with tumor infiltrating lymphocytes and interleukin-2 completed a retrospective, cross-sectional health related quality of life instrument. Established reference populations with other chronic medical conditions, or breast, prostate or other cancers were used for comparison of health related quality of life scores. General health related quality of life was measured with a RAND 36-Item Health Survey 1.0. Cancer targeted quality of life was measured with the Cancer Rehabilitation Evaluation System-Short Form. Sociodemographic and co-morbidity variables were also collected. RESULTS: General health related quality of life in patients treated with tumor infiltrating lymphocytes and interleukin-2 was significantly better than that in heart failure patients on 1 of 8 scales but significantly worse than in the general population on 6 of 8 scales. General health related quality of life in the former patients was also significantly worse than in those with hypertension on 5 of 8 scales and significantly worse than in diabetics on 2 scales. Cancer targeted health related quality of life in patients given immunotherapy was significantly better than in men with prostate cancer on 1 of 5 scales, significantly better than in women with breast cancer on 2 of 5 scales and significantly better than patients with other cancers (nonbreast and nonprostate) on 3 of 5 scales. CONCLUSIONS: Patients undergoing nephrectomy and adjuvant tumor infiltrating lymphocytes plus interleukin-2 therapy for advanced renal cell carcinoma report better health related quality of life than those with other malignancies and better physical function than patients with congestive heart failure. However, health related quality of life is worse than in the general population and similar or worse than in patients with hypertension or type II diabetes. This surveyed population is selective and may represent the best responders among survivors of a highly toxic therapy. Nevertheless, quality and quantity of life should be addressed with patients when considering immunotherapy for metastatic kidney cancer.

Carcinoma, Renal Cell↗
PubMed2006

Activating mutations of Gsalpha in kidney cancer.

PURPOSE: Heterotrimeric G proteins are signal transduction proteins coupled to hormone receptors that activate intracellular second messenger systems, mainly cyclic adenosine monophosphate mediated protein kinase. Recent studies indicate that G proteins may have a major role in oncogenesis as well as in tumor invasiveness and cell proliferation. The involvement of G proteins was formerly thought to be limited to hormonal signal transduction. Activating Gsalpha mutations have been reported in tumors arising only from highly specialized endocrine tissue, such as pituitary adenomas, toxic thyroid adenomas and differentiated thyroid carcinomas, but never in other nonendocrine tumors. We hypothesized that a constitutive activation of this pathway, that is activated Gsalpha and inhibited Gialpha, could be implicated in kidney cancers. We searched for alterations on the Gsalpha gene GNAS and the Gialpha gene in renal cell carcinoma. MATERIALS AND METHODS: Using nested polymerase chain reaction, enzyme digestions, laser microdissection and direct sequencing we looked for activating mutations on GNAS codons 201 and 227, and inhibiting mutations on the Gialpha gene in 30 consecutive patients with clear cell renal cell carcinoma between January 2003 and January 2004. RESULTS: Somatic (tumor specific) activating mutations of Gsalpha were present in a significant proportion of human clear cell renal cell carcinomas. Activating mutations were identified in 5 of the 30 patient DNA preparations (16.6%) with a substitution of arginine 201 by cysteine in 3 and histidine in 2. CONCLUSIONS: These findings suggest the implication of this pathway in human oncogenesis. It may provide a potential therapeutic approach to these frequent and aggressive tumors.

Adult↗