I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy.

I-SPY 2 (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2) is a process targeting the rapid, focused clinical development of paired oncologic therapies and biomarkers. The framework is an adaptive phase II clinical trial design in the neoadjuvant setting for women with locally advanced breast cancer. I-SPY 2 is a collaborative effort among academic investigators, the National Cancer Institute, the US Food and Drug Administration, and the pharmaceutical and biotechnology industries under the auspices of the Foundation for the National Institutes of Health Biomarkers Consortium.

Evaluation of PCR, IEF and ELISA techniques for the detection and identification of potato cyst nematodes from field soil samples in England and Wales.

Effective management of potato cyst nematodes (PCNs) requires simple, rapid and accurate identification and quantification of field populations. Soil samples from a survey of 484 fields in potato rotations in England and Wales were used to compare the identification and quantification of PCNs using IEF, PCR, ELISA and bait plant tests. The cyst counts and bait plant test revealed that 64.3% of field samples contained PCNs. Bait plant tests increased the detection rate of PCNs in field samples by 4-6.4%. This means that some infestations are cryptic and would not normally be detected by standard counts. IEF, PCR and ELISA methods distinguished between Globodera rostochiensis and G pallida and were able to register mixed populations; however they were not in full agreement. All methods suggested that G pallida is the dominant species in the field samples tested. The PCR results indicated that 66% of field samples contained pure G pallida, 8% contained pure G rostochiensis and 26% contained mixtures of the two species. Estimates of the relative process times taken per sample in the PCR, IEF and ELISA techniques are given.

Effects of thymosin on cytotoxicity and virus production in AKR mice.

The cytotoxic potential and ability to produce endogenous ecotropic virus(es) of thymic-, splenic-, and lymph node-derived lymphocytes were significantly (and differentially) altered following thymosin treatment of young (nonleukemic) and aged (preleukemic) AKR mice. Thymosin administration markedly enhanced the cytotoxic potential of both splenic and lymph node lymphocytes from aged animals, but effected a moderate increase only in the spleens of young mice. Thymosin enhanced the production of endogenous virus(es) by thymocytes from aged mice, with the opposite effect noted in young animals. Splenectomy generally reduced the cytotoxic activity and virus titers of lymphocytes from both groups, and thymosin administration further reduced the cytotoxic response. These findings probably reflect overall effects on both regulatory lymphocyte subpopulations and different endogenous viruses in young and aged mice.

Chemotherapy of human tumor xenografts in genetically athymic mice.

A series of studies were undertaken to evaluate the chemotherapeutic response to various antineoplastic drugs of human breast (MX-1) or colon (CX-2) tumor xenografts growing in genetically athymic (nude) mice. Fragments (2mm3) of either tumor type were implanted subcutaneously into the subaxillary region of NIH Swiss nude mice, and single drug therapy was started when tumors became palpable and were growing progressively. 5-Fluorouracil (5-FU) administered on a Q7DX3 schedule starting on Day 21 post tumor implantation elicited significant retardation in the growth rate of CX-2 tumor. A single treatment with methyl-CCNU induced temporary tumor regression. Against MX-1 tumor, both cyclophosphamide and melphalan induced tumor regressions with no recurrence. 5-FU slowed but did not arrest growth of MX-1 tumor. These tumor systems grown in nude mice appear to be suitable models for in vivo screening of anticancer agents that would prove clinically active.