The Treatment of Renal Cell Carcinoma with Human Leukocyte Alpha-Interferon

deKernion, Jean B.; Sarna, G; Figlin, Robert A.; Lindner, Arie; Smith, Robert B.

doi:10.1016/s0022-5347(17)51686-9

Cited by 168 publications

(48 citation statements)

References 5 publications

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“…Interferon (IFN)-␣ was the first cytokine that was studied in patients with mRCC, demonstrating responses in up to 26% of patients [34,35]. Shortly thereafter, reports of CRs also were found with interleukin (IL)-2-based treatments in up to 13% of patients [36,37].…”

Section: Discovery Of New and More Effective Treatmentsmentioning

confidence: 99%

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

2011

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In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed. The Oncologist 2011;16(suppl 2):4 -13

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Section: Discovery Of New and More Effective Treatmentsmentioning

confidence: 99%

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

2011

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“…Immunotherapies using interferons and interleukin 2 have been used for advanced RCC. However, the two therapies alone as well as in conjunction have demonstrated disappointing success rates of 20% or less (4). RCC is a typical hypervascular tumor, and neovascularisation is thought to play a principal role in tumor progression (5).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma

Kudo

Konda²,

Obara³

et al. 2007

Oncol Rep

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Abstract. This study was designed to elucidate the therapeutic effect of transfering the brain-specific angiogenesis inhibitor 1 (BAI1) gene to a mouse renal cell carcinoma cell line (Renca). Female BALB/c mice were inoculated subcutaneously with wild-type Renca (Renca/Wild) cells or Renca cells transfected with the BAI-1 (Renca/BAI-1) or LacZ (Renca/LacZ) gene. Tumor growth was observed every other day from 3 to 35 days after implantation. Moreover, the intratumoral injection of the adenovirus vector containing the gene encoding BAI1 was conducted at two-day intervals from 11 to 31 days after implantation of the Renca/Wild or Renca/BAI1 tumor. Tumor blood flow was measured by colorimetric angiogenesis assay (CAA). The concentration of the vascular endothelial growth factor (VEGF) in the cell culture supernatants was determined by enzyme-linked immunoassay. The size of the Renca/BAI1 tumor was significantly (p<0.01) suppressed compared to the Renca/ Wild and Renca/LacZ tumors 21 days after tumor implantation. The injection of the BAI1 viral vector at 2-day intervals significantly inhibited the growth of both the Renca/Wild and Renca/BAI1 tumors. The blood volume measured by CAA and microvessel density was significantly lower in the Renca/BAI1 than in the Renca/Wild and Renca/LacZ tumors (p<0.01 and p<0.05, respectively). A significant (p<0.01) reduction in VEGF concentration in the supernatant was demonstrated in the Renca/BAI1 compared with the Renca/Wild and Renca/LacZ cell cultures. These observations suggest that the transfer of the BAI1 gene to Renca can suppress the tumor growth via the inhibition of angiogenesis. The down-regulation of VEGF production in tumor cells contributes to this anti-tumor effect.

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“…40% aller Patienten bereits bei Diagnosestellung Metastasen aufweisen [21], daß ungefähr 50% der Patienten mit einem vermeintlich lokalisierten Nierenkarzinom trotz radikaler Tumornephrekto mie an ihren Metastasen versterben [19,20], daß aufgrund unse rer eigenen Erfahrung 80% der Patienten im Stadium I -III innerhalb von 5 Jahren Metastasen entwickeln und letztlich an ihrem Tumor versterben [13] und daß weder eine effektive Zyto statika-noch Hormontherapie existiert [2,3]. 1983 berichteten Queseda et al [16] und De Kernion et al [4] über positive Ergebnisse in der Behandlung von metastasieren den Nierenkarzinomen mit a-2-Interferon. Durch diese Berichte ermutigt, haben wir 2 klinische Phase-II-bzw.…”

Section: Introductionunclassified

Die Behandlung des metastasierenden Nierenkarzinoms mit rekombinantem α-2- oder γ -Interferon

Otto

Schneider²,

Denkhaus³

et al. 1988

Oncol Res Treat

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Im Rahmen zweier klinischer Phase-II- bzw. -III-Studien wurden Patien-ten mit einem histologisch gesicherten metastasierendem Nierenkarzinom entweder mit γ-Interferon in zwei unterschiedlichen Dosierungen (100 μg/m² 3 × pro Woche über 4 h i.v. jede 2. Woche, oder 500 μg/m², 5 × pro Woche über 24 h i.v. jede 2. Woche) oder mit α-2-Interferon allein (18 × 10⁶ E 3 × pro Woche, jede Woche i.m.) oder in Kombination mit Vinblastin (0,1 mg/kg Körpergewicht i.v. jede 3. Woche) behandelt. Ziel dieser Studie war es, die Ansprechrate, die Ansprechdauer, die Überlebensrate, die Toxizität sowie die Verträglichkeit beider Therapie-formen zu eruieren. Die Ansprechrate lag in der γ-Interferonstudie beí beiden Dosierungen insgesamt bei 30%, in der Studie mit α-Interferon in Kombination mit Vinblastin bei insgesamt 31%. Die Ansprechdauer lag in der γ-Interferon-Studie bei 2–34+Monaten, bei der α-2-Interferon-Studie bei 2–24 + Monaten. Patienten, die unter der γ-Interferon-Therapie eine Tumorreaktion auf-wiesen, überlebten statistisch signifikant länger als diejenigen, die nicht auf die Therapie ansprachen (p = 0,0056). Die Behandlung mit der nie-drigen Dosis des γ-Interferon sowie mit α-2-Interferon war ambulant gut durchführbar. Die Interferon-Therapie stellt u. E. derzeit bei Patienten mit einem metastasierenden Nierenkarzinom die Therapie der Wahl dar.

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The Treatment of Renal Cell Carcinoma with Human Leukocyte Alpha-Interferon

Cited by 168 publications

References 5 publications

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

Tumor Biology and Prognostic Factors in Renal Cell Carcinoma

Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma

Die Behandlung des metastasierenden Nierenkarzinoms mit rekombinantem α-2- oder γ -Interferon

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