Faculty Bibliography

Two Tetrahymena kinesin-like proteins (klps) of the kinesin II subfamily, Kin1 and Kin2, were first identified by Brown et al. [1999: Mol Biol Cell 10: 3081-3096] and shown to be involved in ciliary morphogenesis probably as molecular motors in intraciliary transport (ICT). Using Tetrahymena genomic DNA as a template, we cloned Kin5, another kinesin II subfamily member. Kin5 is upregulated upon deciliation, suggesting that Kin5 is a ciliary protein. Kin5 is most closely related to Osm3, a Caenorhabditis elegans kinesin II; Osm3 and Kin5 have a 56% identity, which rises to 60.4% in the motor domain and a 45% identity in a 60 amino acid region of the C-terminal FERM (4.1, Ezrin, Radixin, Moesin) domain, not present in Kin1 or Kin2, which we hypothesize to be a critical domain either for dimerization or for cargo recognition in ICT. An antibody to a peptide sequence from the tail region of Kin5 localizes in a punctate pattern along the ciliary axoneme, colocalizing with an antibody to the raft protein IFT139. These findings suggest that Kin5 is an ICT motor like Osm3. Osm3 orthologs apparently transport membrane proteins and Kin5 may be the homodimeric kinesin II that performs this function in Tetrahymena cilia

PURPOSE: This study was performed to determine whether endoanal ultrasound could be used to accurately stage patients with squamous-cell carcinoma of the anal canal and to determine the response of these tumors to multimodality therapy. METHODS: Thirteen consecutive patients with biopsy-proven squamous-cell carcinoma of the anal canal between 1996 and 1999 were included in the study. All patients underwent a pretreatment staging endoanal ultrasound with a B&K 3535 ultrasound machine using the 1850 rotating 360 degrees probe with a 10-MHz transducer. Tumors were staged using our own modification of a 1984 TNM staging system. For our study, a uT1 tumor was confined to the submucosa; a uT2a lesion invaded only the internal anal sphincter; a uT2b lesion penetrated into the external anal sphincter; a uT3 lesion invaded through the sphincter complex into the perianal tissues; and a uT4 lesion invaded adjacent structures. After the initial study, patients decided on a course of treatment, either primary surgery or chemoradiation. For patients choosing chemoradiation, a clinical examination with biopsies and a repeat endoanal ultrasound was performed after completion of therapy. Findings on physical examination and biopsy results were compared with the follow-up endoanal ultrasound. For those choosing surgery, the pathology specimen from the abdominoperineal resection was reviewed and compared with the initial endoanal ultrasound interpretation to determine the accuracy of endoanal ultrasound staging. RESULTS: One patient died of complications from acquired immunodeficiency syndrome before undergoing definitive treatment for his anal cancer. Of the remaining 12 patients who comprised the study, the endoscopic staging was as follows: 1 uT1, 5 uT2a, 3 uT2b, 2 uT3, and 1 uT4. Five of the 12 patients selected surgery as the primary treatment modality for their disease. The other seven patients underwent a full course of chemoradiation. In all five patients who had an abdominoperineal resection, the surgical staging correlated with the endoanal ultrasound staging (2 T2a tumors and 3 T2b tumors). In the remaining seven patients, six to eight weeks after completion of therapy, there was no evidence of residual tumor by clinical examination and biopsies. In one of the seven patients, no abnormalities were detected on endoanal ultrasound, and it was interpreted as normal with no evidence of disease. In the remaining six patients, endoanal ultrasound revealed abnormalities that were judged to represent radiation-induced changes rather than residual disease. A repeat endoanal ultrasound was done in these patients two to four months after the biopsies. Complete resolution of the postradiation changes occurred in all patients, and the scans were interpreted as showing no evidence of disease. CONCLUSIONS: Endoanal ultrasound can accurately determine the depth of penetration of squamous-cell carcinoma into the sphincter complex and can be used to gauge accurately the response of these tumors to chemoradiation therapy. Our newly proposed ultrasound staging system may be more useful in choosing treatment options; future studies should be aimed at using endoanal ultrasound in identifying early lesions that may be amenable to less aggressive therapy as well as determining the utility of ultrasound in the surveillance of patients after successful treatment of their initial tumors