Prognosis of Intravesical Bacillus Calmette-Guerin Therapy for Superficial Bladder Cancer by Immunological Urinary Measurements: Statistically Weighted Syndromes Analysis

Jackson, Andrew M.; Ivshina, Anna V.; Sen’ko, O. V.; Кузнецова, А. В.; SUNDAN, A.; O’Donnell, Michael A.; Clinton, Steven K.; Alexandroff, A.B.; SELBY, P.J.; James, Keith; Kuznetsov, V. A.

doi:10.1016/s0022-5347(01)63835-7

Cited by 42 publications

(31 citation statements)

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“…PAM is a modification of the nearest-centroid method and was applied as previously described (25). SWS is a supervised, combinatorial pattern recognition method based on a statistical voting procedure that uses selected subsets of predictors that act alone or in combination (26,27). Briefly, the methodology is based on several steps: (a) optimal recoding of the given covariates to obtain discrete-valued variables; (b) selection of the most informative and statistically robust of these discrete-valued variables and their combinations (termed syndromes) that best characterize the classes of interest; (c) tallying the statistically weighted ''votes'' of these syndromes to compute the value of the outcome prediction function (by leave-one-out cross-validation).…”

Section: Methodsmentioning

confidence: 99%

Genetic Reclassification of Histologic Grade Delineates New Clinical Subtypes of Breast Cancer

et al. 2006

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Histologic grading of breast cancer defines morphologic subtypes informative of metastatic potential, although not without considerable interobserver disagreement and clinical heterogeneity particularly among the moderately differentiated grade 2 (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade 1 (G1) and grade 3 (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with G2 disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays. Using class prediction algorithms, we identified 264 robust grade-associated markers, six of which could accurately classify G1 and G3 tumors, and separate G2 tumors into two highly discriminant classes (termed G2a and G2b genetic grades) with patient survival outcomes highly similar to those with G1 and G3 histology, respectively. Statistical analysis of conventional clinical variables further distinguished G2a and G2b subtypes from each other, but also from histologic G1 and G3 tumors. In multivariate analyses, genetic grade was consistently found to be an independent prognostic indicator of disease recurrence comparable with that of lymph node status and tumor size. When incorporated into the Nottingham prognostic index, genetic grade enhanced detection of patients with less harmful tumors, likely to benefit little from adjuvant therapy. Our findings show that a genetic grade signature can improve prognosis and therapeutic planning for breast cancer patients, and support the view that low-and high-grade disease, as defined genetically, reflect independent pathobiological entities rather than a continuum of cancer progression.

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Section: Methodsmentioning

confidence: 99%

Genetic Reclassification of Histologic Grade Delineates New Clinical Subtypes of Breast Cancer

et al. 2006

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“…cancer therapy ͉ immunotherapy ͉ tumor homing A lthough reports of using bacteria to treat tumors in humans date as far back as to 1893 (1), thus far, microbial-based approaches to cancer immunotherapy are limited to use of bacillus Calmette-Guérin (BCG) for superficial bladder carcinomas (2,3). It has been reported that bacteria administered by i.v.…”

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confidence: 99%

AttenuatedSalmonellaengineered to produce human cytokine LIGHT inhibit tumor growth

Loeffler

Le'Negrate

Krajewska

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

156

105

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Intravenously administered bacteria reportedly accumulate in tumors. Furthermore, systemic administration of attenuated Salmonella typhimurium has little or no significant side-effects in humans. Consequently, we engineered such bacteria to improve their oncolytic activity by stably inserting a gene encoding LIGHT, a cytokine known to promote tumor rejection. Unlike control bacteria, attenuated S. typhimurium expressing LIGHT inhibited growth of primary tumors, as well as the dissemination of pulmonary metastases, in various mouse tumor models employing murine carcinoma cell lines in immunocompetent mice. Antitumor activity was achieved without significant toxicity and was associated with infiltration of inflammatory cells and dependent on the LIGHT receptors, herpes virus entry mediator (HVEM), and lymphotoxin-␤ receptor (LT␤R). These findings provide evidence that nonvirulent bacteria can be exploited as targeting vehicles for local generation of therapeutic proteins in tumors.cancer therapy ͉ immunotherapy ͉ tumor homing

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“…The use of live bacteria for the treatment of cancer has thus far been limited to bacillus Calmette-Guérin (BCG) for the treatment of superficial bladder carcinomas and is administered by urethral catheterization [7]. Although the mechanism of action is unknown, it is thought that BCG works by induction of anti-tumor immunity attributable to the inflammatory response and production of cytokines following BCG administration [8].…”

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confidence: 99%

Biodistribution and Genetic Stability of the Novel Antitumor Agent VNP20009, a Genetically Modified Strain ofSalmonella typhimurium

et al. 2000

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VNP20009 is a genetically modified strain of Salmonella typhimurium possessing an excellent safety profile, including genetically stable attenuated virulence (a deletion in the purI gene), reduction of septic shock potential (a deletion in the msbB gene), and antibiotic susceptibility. VNP20009 is genetically stable after multiple generations in vitro and in vivo. In mice, VNP20009 is rapidly cleared from the blood from a peak level of 1x104 cfu/mL to undetectable levels in 24 h. In tumor-bearing mice, VNP20009 accumulates preferentially in tumors over livers at a ratio of 1000&rcolon;1. In nonhuman primates, VNP20009 was also rapidly cleared from the blood, from a peak level of 1.0x106 cfu/mL to undetectable levels in 24 h. VNP20009 was detected in the liver, spleen, and bone marrow of monkeys; the amount decreased over time, and VNP20009 was cleared from all organs by day 41; no VNP20009 could be detected in the urine or feces of the monkeys. VNP20009 is genetically stable after many generations of growth (>140) both in vitro and in vivo.

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Prognosis of Intravesical Bacillus Calmette-Guerin Therapy for Superficial Bladder Cancer by Immunological Urinary Measurements: Statistically Weighted Syndromes Analysis

Cited by 42 publications

References 0 publications

Genetic Reclassification of Histologic Grade Delineates New Clinical Subtypes of Breast Cancer

Genetic Reclassification of Histologic Grade Delineates New Clinical Subtypes of Breast Cancer

AttenuatedSalmonellaengineered to produce human cytokine LIGHT inhibit tumor growth

Biodistribution and Genetic Stability of the Novel Antitumor Agent VNP20009, a Genetically Modified Strain ofSalmonella typhimurium

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