Clin Cancer Res
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Randomized Controlled Trial Comparative Study
Phase I study of combined pegylated liposomal doxorubicin with protracted daily topotecan for ovarian cancer.
To determine the maximum tolerated dose and dose-limiting toxicity of Doxil with low-dose continuous infusion topotecan and subsequently with low-dose oral topotecan. Other specific aims were preliminary assessment of activity in advanced ovarian and tubal malignancies, pharmacokinetics of oral topotecan, and correlation of response with topoisomerase I and II expression in tumors. ⋯ Doxil with 14-day topotecan infusion is a well-tolerated regimen and suitable for study in platinum-resistant or refractory ovarian or tubal cancers. Frequent gastrointestinal toxicity and/or erratic absorption complicate treatment with a longer topotecan infusion or with oral topotecan, respectively, and these combinations are not recommended.
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To present the basis of the decision of the Food and Drug Administration to grant accelerated approval for letrozole for extended adjuvant treatment of early-stage breast cancer in postmenopausal women after completion of adjuvant tamoxifen. ⋯ Letrozole administration led to a statistically significant prolongation in disease-free survival. Fractures and cardiovascular events were similar to placebo; however, new diagnoses of osteoporosis were more frequent. Short duration of treatment and follow-up precluded assessment of long-term safety and efficacy. Thus, accelerated approval was granted instead of regular approval.
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Comparative Study
Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women.
Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown. ⋯ Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.
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Comparative Study
Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer.
Fructose 2,6-bisphosphate (F2,6BP) is a potent activator of phosphofructokinase, which is a rate-limiting enzyme of glycolysis. The concentration of F2,6BP depends on the activity of the bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase). Four genes encoding PFK-2/FBPase have been identified and termed PFKFB1 to PFKFB4. PFKFB3 protein is expressed in high levels in human tumors in situ. The purpose of this study was to determine the role of functional interactions between the phosphorylation of PFKFB3 and activated glycolysis in human cancer cells. ⋯ These findings support a potential role for the phosphorylation of PFKFB3 protein in the progression of cancer and angiogenesis.
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To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). ⋯ Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.