Clin Cancer Res
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Platinum-DNA adducts can be measured in peripheral blood leukocytes during platinum-based chemotherapy, and high adduct levels have been correlated with favorable clinical response in patients with germ cell cancer. Twenty-five patients with advanced germ cell cancer were treated with platinum-based chemotherapy regimens using the same dose and schedule of cisplatin. Platinum-DNA adducts were measured by atomic absorption spectrometry on the first and fifth days of the first cycle of cisplatin-based therapy. ⋯ Twenty-three patients had day 5 adduct levels measured. The mean day 5 adduct level in the 15 patients who were alive and without progression was 62.133 fmol/microgram compared to 153.50 fmol/microgram in the patients who were dead or progressing (two-sided P = 0.02). Contrary to previous reports, these data indicate that high platinum-DNA adduct levels do not correlate with favorable outcome in patients with advanced germ cell cancer.
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We assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and 16alpha-[18F]fluoro-17beta-estradiol (FES) in women with breast cancer for predicting response to systemic therapy. Results of FES-PET were correlated with estrogen receptor (ER) status. Forty-three women with locally advanced or metastatic breast cancer underwent FDG-PET and FES-PET prior to institution of systemic therapy. ⋯ In our experience, FDG-PET imaging is more sensitive than conventional imaging methods, including computed tomography, in staging women with breast cancer. When compared with the in vitro assay of ER status, FES-PET has an apparent sensitivity of 76% and specificity of 100%. Our finding of a subset of patients who have tumors that are ER+ and FES- suggests that the functional assessment of hormone sensitivity by PET imaging can identify patients with ER+ disease whose tumors are likely to be hormone refractory.
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Retinoids have been shown to act as cytostatic agents against a variety of tumor cell types, including squamous carcinoma cells. Recently it was reported that certain retinoids can induce apoptosis as well. Because we are investigating the potential of retinoids in chemoprevention and therapy for head and neck premalignant and malignant lesions, we compared the effects of all-trans-retinoic acid (ATRA) and N-(4-hydroxyphenyl)retinamide (4HPR) on seven human head and neck squamous cell carcinoma cell lines (17A, 17B, 22A, 22B, 38, SqCC/Y1, and 1483). ⋯ In 17B cells, a clear DNA ladder was observed as early as 2 days after treatment with 4HPR; however, neither ATRA nor 9-cis-retinoic acid was as effective. In addition, morphological changes associated with apoptotic cell death, such as chromatin condensation and nuclear segmentation, were observed by propidium iodide staining and by electron microscopic analysis after 4HPR treatment. These results demonstrate that 4HPR causes apoptosis in several head and neck squamous cell carcinoma cell lines and that it is more potent in this effect than ATRA.
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A murine model in which to study multiple drug resistance in human hepatocellular carcinoma was developed. PRF/PLC/5 hepatoma cells (Alex 0) and an induced multidrug resistant clone (Alex 0.5) were injected intrasplenically into severe combined immunodeficiency mice. In 70% of injected mice, hepatoma cells engrafted in the liver and grew as intrahepatic metastasis. ⋯ The effect was most pronounced in mice bearing Alex 0.5 tumors. Immunoblotting of tumors which initially responded to MRK16 therapy, but subsequently relapsed, revealed a marked decrease in P-glycoprotein expression when compared to results in tumors that were untreated or treated with vinblastine or control antibody. In summary, we have developed an intrahepatic tumor xenograft model of human hepatocellular carcinoma in mice that permits noninvasive serial quantification of tumor burden by determination of serum HBsAg levels and demonstrated a positive response to immunotherapy with anti-P-glycoprotein antibodies.
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A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. ⋯ The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with