Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization.
PTH (7-84) has antagonistic effects on the calcemic and phosphaturic actions of PTH (1-84) whole molecule (bioPTH). Human plasma contains bioPTH and PTH (7-84)-like fragments. Using bioPTH-specific and nonspecific assays, we found that the patients with pseudohypoparathyroidism (PHP) type I with PTH-resistant hypocalcemia and hyperphosphatemia had the increased plasma levels of bioPTH and PTH (7-84)-like fragments than normal subjects (26.8 +/- 13.2 vs. 2.37 +/- 0.75 pmol/liter, P < 0.01 and 16.2 +/- 8.8 vs. 0.82 +/- 0.47 pmol/liter, P < 0.01, respectively). Calcitriol treatment increased phosphaturic response to PTH (1-34) (P < 0.05), and there was a negative correlation between phosphaturic response and the PTH levels (P < 0.05). These results suggested that the increased bioPTH and PTH (7-84)-like fragment levels may be related to the impaired phosphaturic response to PTH (1-34) in PHP type I. We also examined bioPTH-calcium dynamics in PHP type Ib patients and found that set-point calcium was 0.928 +/- 0.045 mmol/liter and the baseline to maximal ratio of bioPTH was 0.96 +/- 0.04. Calcitriol treatment increased set-point calcium to 1.129 +/- 0.028 mmol/liter (P < 0.01) and suppressed baseline to maximal ratio of bioPTH to 0.35 +/- 0.21 (P < 0.01). These bio-PTH calcium dynamics studies revealed the maximally stimulated baseline PTH secretion in PHP type Ib and demonstrated the effects of calcitriol on PTH-calcium curve shift and the degree of relative stimulation of baseline secretion.
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