hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for immunotherapy of uterine serous papillary carcinoma

BACKGROUND: Uterine serous papillary adenocarcinoma (USPC) is a highly aggressive variant of endometrial cancer. Human immunoconjugate molecule (hI-con1) is an antibody-like molecule targeted against tissue factor (TF), composed of two human Factor VII (fVII) as the targeting domain, fused to human immunoglobulin (Ig) G1 Fc as an effector domain. We evaluated hI-con1 potential activity against primary chemotherapy-resistant USPC cell lines expressing different levels of TF. METHODS: A total of 16 formalin-fixed, paraffin-embedded USPC samples were evaluated by immunohistochemistry (IHC) for TF expression. Six primary USPC cell lines, half of which overexpress the epidermal growth factor type II (HER2/neu) receptor at 3\ufe levels, were assessed by flow cytometry and real-time PCR for TF expression. Sensitivity to hI-con1-dependent cell-mediated cytotoxicity (IDCC) was evaluated in 5-hour-chromium release assays. Finally, to investigate the effect of interleukin-2 (IL-2) on IDCC, 5-h 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50\u2013100 IU ml 1). RESULTS: Cytoplasmic and/or membrane TF expression was observed in all 16 (100%) USPC samples tested by IHC, but not in normal endometrium. High expression of TF was found in 50% (three out of six) of the USPC cell lines tested by real-time PCR and flow cytometry when compared with normal endometrial cells (NECs; Po0.001). Uterine serous papillary adenocarcinoma cell lines overexpressing TF, regardless of their high or low HER2/neu expression, were highly sensitive to IDCC (mean killing\ub1s.d., 65.6\ub13.7%, range 57.5\u201377.0%, Po0.001), although negligible cytotoxicity against USPC was seen in the absence of hI-con1 or in the presence of Rituximab control antibody. The addition of low doses of IL-2 further increased the cytotoxic effect induced by hI-con1 against chemotherapy-resistant USPC. CONCLUSION: hI-con1 induces strong cytotoxicity against primary chemotherapy-resistant USPC cell lines overexpressing TF. The hI-con1 may represent a novel therapeutic agent for the treatment of patients harbouring advanced, recurrent and/or metastatic USPC refractory to standard treatment modalities

EXAFS Study of the Local Iodine Structure in C60(I2)x and in C70(I2)x

Iodine LI,III - and K-edge XANES and EXAFS are employed to study the local structure of molecular iodine in C60(I2)x and C70(I2)x in the temperature range 20 K - 300 K. The K-edge EXAFS analysis, when compared with LIII-EXAFS, provides more detailed information about intra- and intermolecular distances

EXAFS Study of the Local Iodine Structure in C60(I2)xC_{60} (I_2)_x and in C70(I2)xC_{70} (I_2)_x

Iodine LI,III - and K-edge XANES and EXAFS are employed to study the local structure of molecular iodine in C60(I2)x and C70(I2)x in the temperature range 20 K - 300 K. The K-edge EXAFS analysis, when compared with LIII-EXAFS, provides more detailed information about intra- and intermolecular distances

Gd–LIII EXAFS study of structural and dynamic properties of Gd@C82\mathrm{Gd@C_{82}} between 10 and 300 K

The location of endohedral Gd ions in Gd@C82 is studied by Gd–LIII X-ray absorption spectroscopy in the temperature range 10–300 K. The near-edge data point to a covalent bond of trivalent Gd ions with the carbon cage. The EXAFS data can be well fitted with a Gd position above a carbon hexagon with two neighbour shells of carbon at distances R1,2=2.49(3) and 2.95(5) Å, corresponding to a large off-center position of about 1.8 Å from the center of the C82 cage. The second cumulants of these distances are relatively large and weakly depending on temperature. This points to a considerable distribution in Gd–C1 and Gd–C2 distances and confirms the relatively strong binding of the Gd ion to the C82 cage. These results will be discussed together with previous EXAFS studies and theoretical calculations of Y@C82 and La@C82

161Dy\mathrm{^{161}Dy} Mössbauer study of the endohedral metallofullerenes Dy@Cn(n=80,82,84)\mathrm{Dy@C_n(n = 80, 82, 84)}

Mössbauer studies of Dy@Cn (n = 80, 82, 84) metallofullerenes were performed at 4.2, 9.6 and 78 K with the 161Dy (25.6 keV) resonance. The observed spectra consist of two subspectra splitted by magnetic hyperfine fields near to the full moment value of trivalent Dy. Paramagnetic relaxation is observed even at 4.2 K. The observed isomer shift is consistent with the Dy3+ state and indicates a full charge transfer to the fullerene cage