Aspects of treating cancer with anticholinergic agents are the subject of a patent ("Hybrid cholinergic agents and compositions, methods of making, and methods of using to treat a cholinergic disorder," US 6,624,155) issued on September 23, 2003, to the University of Arkansas; JPR is an inventor on this patent. JPR owns equities related to health care (Agile Therapeutics, Gilead Sciences, Merck, Proctor & Gamble).
A unifying feature of polycystin-2 channels is their localization to both primary and motile cilia/flagella. In Drosophila melanogaster, the fly polycystin-2 homologue, Amo, is an ER protein early in sperm development but the protein must ultimately cluster at the flagellar tip in mature sperm to be fully functional. Male flies lacking appropriate Amo localization are sterile due to abnormal sperm motility and failure of sperm storage. We performed a forward genetic screen to identify additional proteins that mediate ciliary trafficking of Amo. Here we report that Drosophila homologues of KPC1 and KPC2, which comprise the mammalian KIP1 ubiquitination-promoting complex (KPC), form a conserved unit that is required for the sperm tail tip localization of Amo. Male flies lacking either KPC1 or KPC2 phenocopy amo mutants and are sterile due to a failure of sperm storage. KPC is a heterodimer composed of KPC1, an E3 ligase, and KPC2 (or UBAC1), an adaptor protein. Like their mammalian counterparts Drosophila KPC1 and KPC2 physically interact and they stabilize one another at the protein level. In flies, KPC2 is monoubiquitinated and phosphorylated and this modified form of the protein is located in mature sperm. Neither KPC1 nor KPC2 directly interact with Amo but they are detected in proximity to Amo at the tip of the sperm flagellum. In summary we have identified a new complex that is involved in male fertility in Drosophila melanogaster.
Bone scan has been widely employed to detect osteoblastic bone metastasis because of the imaging technique's high sensitivity. However, care should be taken to distinguish false positive bone lesions which result from microcalcification of soft tissue malignancy with real osseous metastasis by correlating other modalities of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). We report, for the first time, a patient who was initially diagnosed with stage II left breast infiltrating ductal carcinoma and was under clinical management for 20 years. The patient subsequently presented with thoracic symptoms. Bone scan showed multiple focal uptakes within bilateral thoracic ribs. FDG PET/CT scans, however, showed numerous metabolically active bilateral pulmonary nodules with no osseous lesions in ribs. This case demonstrates abnormal findings on bone scans mimicking metastatic rib lesions from micro-calcified pulmonary metastatic nodules in a patient with breast cancer. Thus, care should be taken to correlate interpretation of high sensitivity but non-specificity bone imaging with other modalities such as FDG PET/CT.
Keywords:Whole body bone scan; FDG PET/CT; Breast cancer; Pulmonary metastasis; Bony metastasis
SummaryTc-99m MDP whole body bone scan is very sensitive and widely applied for clinical staging, monitoring therapeutic response, and evaluating malignant tumor recurrence in patients with malignant cancers, specifically breast cancer in female patients, prostate cancer in male patients, and other cancers including pulmonary cancers. However, attention should be paid by clinicians when they dictate bone imaging given that the various false positive findings may diminish specificity of the study. We presented a case for the first time that demonstrates abnormal findings on bone scans mimicking metastatic rib lesions from micro-calcified pulmonary metastatic nodules in the patient with breast cancer.
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