The epidermal growth factor-seven transmembrane (EGF-TM7) family is a group of seven-span transmembrane receptors predominantly expressed by cells of the immune system. Family members CD97, EGF ...module-containing mucin-like receptor (EMR) 1, EMR2, EMR3, EMR4, and EGF-TM7-latrophilin-related protein are characterized by an extended extracellular region with a variable number of N-terminal EGF-like domains. EGF-TM7 receptors bind cellular ligands as demonstrated by the interaction of CD97 with decay accelerating factor (CD55) and dermatan sulfate. Investigating the effect of newly generated mAb on the migration of neutrophilic granulocytes, we here report for the first time in vivo data on the function of CD97. In dextran sulfate sodium-induced experimental colitis, we show that homing of adoptively transferred neutrophils to the colon was significantly delayed when cells were preincubated with CD97 mAb. The consequences of this defect in neutrophil migration for host defense are demonstrated in a murine model of Streptococcus pneumoniae-induced pneumonia. Mice treated with CD97 mAb to EGF domain 1 (1B2) and EGF domain 3 (1C5) displayed a reduced granulocytic inflammatory infiltrate at 20 h after inoculation. This was associated with a significantly enhanced outgrowth of bacteria in the lungs at 44 h and a strongly diminished survival. Together, these findings indicate an essential role for CD97 in the migration of neutrophils.
Abstract Purpose The aim of this study was to clinically validate a multivariable normal tissue complication probability (NTCP) model for grade 2–4 swallowing dysfunction at 6 months after ...radiotherapy or chemoradiation (SWALM6 ) in head and neck cancer patients treated with swallowing sparing intensity modulated radiotherapy (SW-IMRT) and to test if SW-IMRT resulted in a reduction of the prevalence of SWALM6. Materials and methods The primary endpoint was SWALM6 . For all 186 patients, a standard IMRT (parotid sparing) and a SW-IMRT plan (additional constraints for swallowing organs at risk) was created. The difference in NTCP for SWALM6 (ΔNTCPSWALM6 = NTCPstandard − NTCPSW-IMRT ) was calculated. Patients were treated with SW-IMRT. The external validation of the NTCP model was analyzed by comparing performance measures. Results The mean ΔNTCPSWALM6 was 4.9% (range 0.01–17.3%), with a significant lower mean predicted NTCPSW-IMRT of 22.6% (95% CI 20.2–24.9%), compared to NTCPstandard of 27.5% (95% CI 24.9–29.9%) ( p < 0.001). There was a perfect correspondence of NTCPSW-IMRT with the observed prevalence of SWALM6 (22.6%). The overall model performance, discrimination and ‘goodness of fit’ were good. Conclusion We externally validated the multivariable NTCP model for SWALM6 in SW-IMRT treated patients, showing reduced swallowing dysfunction by reducing the dose parameters included in this NTCP model.
In 1953, Slaughter et al. D. P. Slaughter et al. , Cancer (Phila.), 6: 963–968, 1953 proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck
(HNSCC) ...and discussed its clinical significance for the development of second primary tumors and local recurrences. To define
the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the
accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five
noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity
in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the
field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected
in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different
subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered
field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that
this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor,
suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered
mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency
of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields
may have profound implications for future patient management.
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