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Notes: Abstract Concomitant chemoradiotherapy with cisplatin and combination chemotherapy in the neoadjuvant setting have both shown promising results.Purpose: To identify a locally and systemically active concomitant chemoradiotherapy regimen incorporating high-dose cisplatin, interferon alfa-2a (IFN), fluorouracil (5-FU), hydroxyurea (HU) and radiotherapy.Methods: Phase I cohort design establishing the maximal tolerated dose (MTD) of cisplatin with and without granulocyte colony stimulating factor (GCSF). For the first six dose levels, a 4-week cycle consisted of escalating doses of cisplatin during weeks 1 and 2, IFN (week 1), and 5-FU and HU (week 2) with single daily radiation fractions of 200 cGy during days 1–5 of weeks 1–3 and no treatment in week 4. When dose-limiting neutropenia was encountered, GCSF was added during weeks 1, 3, and 4. Finally, to decrease esophagitis, the radiotherapy schedule was altered to 150 cGy twice daily during weeks 1 and 2, followed by a 2-week break (level 7).Results: Forty-nine patients with refractory chest malignancies were treated. The MTD of this regimen without GCSF was cisplatin 50 mg/m2 in weeks 1 and 2, IFN 5 million Units (MU)/m2 per day on days 1–5 in week 1, 5-FU 800 mg/m2 per day for 5 days by continuous infusion, and HU 500 mg every 12 h for 11 doses during week 2. The addition of GCSF during weeks 1, 3, and 4 allowed for escalation of cisplatin to 100 mg/m2 during weeks 1 and 2, with a decreased dose of IFN at 2.5 MU/m2 per day to avoid renal toxicity. Dose-limiting toxicity (DLT) included severe neutropenia, thrombocytopenia, and esophagitis in 5 of 13 patients. Increased thrombocytopenia in patients receiving GCSF was not observed. During hyperfractionated radiotherapy (level 7) chemotherapy doses were as above except for a reduction of 5-FU to 600 mg/m2 per day. While severe esophagitis was reduced, grade 4 thrombocytopenia became more prevalent and was seen in 6 of 7 patients. In-field tumor responses were observed in 17 of 28 evaluated patients with non-small-cell lung cancer. The median times to progression and survival were 4 and 6 months, respectively. When only patients with all known disease confined to the radiotherapy field were considered the corresponding times were 6 and 15 months, respectively. Most treatment failures occurred outside of the irradiated field.Conclusions: (1) This intensive multimodality regimen can be given with aggressive supportive care incorporating GCSF. The recommended phase II doses for a 4-week cycle are cisplatin 50 mg/m2 week 1, and 100 mg/m2 week 2, IFN 2.5 MU, HU 500 mg every 12 h×11 and 5-FU 800 mg/m2 per day with single fraction radiotherapy during weeks 1–3 and GCSF during weeks 1, 3, and 4. (2) GCSF can be safely administered and provides effective support of neutrophils when administered simultaneously with IFN, cisplatin, and chest radiotherapy. (3) There is synergistic renal toxicity when high doses of IFN and cisplatin are given together. (4) Hyperfractionated radiotherapy decreases the severity of esophagitis but increases thrombocytopenia. (5) Although highly toxic, response rates, time to progression and survival figures with this regimen are encouraging and support its investigation in the phase II setting.

Notes: Abstract. By means of in situ hybridisation studies, it is shown that parathyroid hormone-related protein (PTHrP) mRNA is strongly expressed in the developing enamel organs of rat teeth. In particular, the cervical loop hybridises strongly with the PTHrP probe and expression is maintained at this site throughout life in the permanently erupting incisor teeth. In mature molar teeth, expression is downregulated to low levels and confined to the epithelial cell rests of Malassez and/or cementoblasts which may derive from these. The gene is also expressed at low levels in the tissue overlying the erupting molars and, thereafter, in the junctional epithelia and connective tissue cells of the epithelial attachment on all tooth surfaces. The premise that PTHrP may undergo post-translational processing and that the resultant products could act in different ways raises the possibility of its exerting multiple paracrine actions during tooth development. These could include the control of cell division and local vascular dilation during development.

Notes: Abstract By means of in situ hybridisation studies, it is shown that parathyroid hormone-related protein (PTHrP) mRNA is strongly expressed in the developing enamel organs of rat teeth. In particular, the cervical loop hybridises strongly with the PTHrP probe and expression is maintained at this site throughout life in the permanently erupting incisor teeth. In mature molar teeth, expression is downregulated to low levels and confined to the epithelial cell rests of Malassez and/or cementoblasts which may derive from these. The gene is also expressed at low levels in the tissue overlying the erupting molars and, thereafter, in the junctional epithelia and connective tissue cells of the epithelial attachment on all tooth surfaces. The premise that PTHrP may undergo post-translational processing and that the resultant products could act in different ways raises the possibility of its exerting multiple paracrine actions during tooth development. These could include the control of cell division and local vascular dilation during development.

Notes: A three-tiered approach involving autoradiography, measurement of seasonal lipid patterns and deployment of in situ microcosms, was used to assess the potential of the moderately lipophilic herbicide triallate to accumulate in two amphipod species (Hyalella azteca and Gammarus lacustris) in two prairie lakes and one prairie pond. Autoradiography revealed that the storage sites for triallate in amphipod tissues were associated with lipid-rich tissues, in particular, with triacylglycerol storage sites and the nervous system. Seasonal lipid patterns (total lipid) of amphipods did not differ amongst sites within a waterbody, however, there were marked differences amongst water bodies. Female amphipods had higher lipid contents than males during the reproductive period in early summer but this difference diminished later in the summer. Bioaccumulation factors of triallate in amphipod tissues ranged from 72 to 80 times the nominal water concentrations in 7 day microcosm trials. Triacylglycerol content and triallate body burden were positively correlated (r 2=0.58–0.91) for H. azteca in the two lakes in which the microcosms were deployed. However, no significant correlations were obtained between triacylglycerol content and triallate body burden for G. lacustris. Triacylglycerol contents in the amphipods were generally highest in spring and autumn, coinciding with application times for triallate.