ABSTRACT
Krüppel-like transcription factor 10 (KLF10), also named as TIEG1, plays essential roles in mediating transforming growth factor beta (TGFß) signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer progression in vivo have yet to be fully characterized. Here, we have employed two well-characterized Pdx-1CreLSL-KrasG12D and Pdx-1CreLSL-KrasG12Dp53L/L pancreatic cancer models to ablate KLF10 expression and determine the impact of KLF10 deletion on tumor development and progression. We show that loss of KLF10 cooperates with KrasG12D leading to an invasive and widely metastatic phenotype of pancreatic ductal adenocarcinoma (PDAC). Mechanistically, loss of KLF10 in PDAC is shown to increase distant metastases and cancer stemness through activation of SDF-1/CXCR4 and AP-1 pathways. Furthermore, we demonstrate that targeting the SDF-1/CXCR4 pathway in the context of KLF10 deletion substantially suppresses PDAC progression suggesting that inhibition of this pathway represents a novel therapeutic strategy for PDAC treatment.
Subject(s)
Carcinoma, Pancreatic Ductal/metabolism , Chemokine CXCL12/metabolism , Early Growth Response Transcription Factors/deficiency , Kruppel-Like Transcription Factors/deficiency , Pancreatic Neoplasms/metabolism , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Chemokine CXCL12/genetics , Early Growth Response Transcription Factors/genetics , Early Growth Response Transcription Factors/metabolism , Humans , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Mice , Mice, Inbred C57BL , Neoplasm Metastasis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Signal Transduction , Survival Rate , Tumor Suppressor Protein p53/geneticsABSTRACT
This article reviews the techniques of motor and sensory nerve conduction studies and needle electromyography methods, which are particularly useful for localizing nerve injuries in upper extremity and hand trauma. Included are details of methods for detecting and quantifying the degree of axon loss and for using this information to make treatment decisions and predict outcomes. The epidemiology and classification of traumatic peripheral nerve injuries, the effects of these injuries on nerve and muscle, and the means by which electrodiagnosis is used to help classify the injury are described. An overview of recovery mechanisms also is presented.
Subject(s)
Electrodiagnosis , Peripheral Nerve Injuries , Action Potentials , Adult , Electromyography , Humans , Male , Motor NeuronsABSTRACT
A 32-year-old man presented with multiple cranial neuropathies and his serum was positive for botulism type B. However, serial electrodiagnostic studies were consistent with a primarily neuropathic process, such as Fisher syndrome, rather than a neuromuscular junction disorder. Electrodiagnostic study findings in patients with presumed neuromuscular junction disorders may mimic findings suggestive of a neuropathic process, or the bioassay for botulism may be falsely positive in patients with Fisher Syndrome.
Subject(s)
Botulism/diagnosis , Miller Fisher Syndrome/diagnosis , Adult , Botulism/blood , Diagnosis, Differential , Electrodiagnosis , Electromyography , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Miller Fisher Syndrome/therapy , Treatment OutcomeSubject(s)
Bone and Bones/diagnostic imaging , Gaucher Disease/diagnostic imaging , Arthrography , Bone and Bones/pathology , Diagnosis, Differential , Epiphyses/diagnostic imaging , Epiphyses/pathology , Fractures, Closed/etiology , Gaucher Disease/complications , Gaucher Disease/diagnosis , Gaucher Disease/pathology , Humans , Joints/pathologyABSTRACT
Ultrasonographic records of 239 patients with unexplained renal insufficiency were reviewed to determine the efficacy of renal ultrasonography as a screening examination. Ninety-five (40%) examinations were normal; 24 (10%) examinations showed no renal lesion, but some important incidental finding was discovered; 120 (50%) examinations showed a renal abnormality, including 24 (10%) that showed bilateral urinary tract obstruction. The discovery of bilateral urinary tract obstruction was of particular importance and, in the majority of cases (16/24), led to some type of definitive interventional procedure. Sonography in patients with renal insufficiency, whether normal or abnormal, provides useful information to the practicing physician with a potentially significant impact on the patient's clinical course.
Subject(s)
Acute Kidney Injury/diagnosis , Ultrasonography , Urologic Diseases/diagnosis , Adult , Aged , Creatinine/blood , Female , Humans , Kidney Diseases/diagnosis , Male , Middle Aged , Urologic Diseases/surgery , Urologic Neoplasms/diagnosisABSTRACT
The maximum diameter of the extrahepatic bile duct visible on cholesonograms was measured immediately before and immediately after endoscopic retrograde cannulation and injection of the biliary and pancreatic ducts (ERCP) in 24 patients. Sonographic bile duct diameter increased by 3 mm or more in nine patients, all of whom had had a previous cholecystectomy. Bile duct diameter was unchanged in the remaining 15 patients, six of whom had had cholecystectomy. The technical performance of ERCP alone will alter bile duct diameter in a significant proportion of patients having endoscopic cannulation of the biliary tree. This is particularly so for patients who have had their gallbladders removed. The true diameter of the extrahepatic bile duct cannot be determined in many patients by simple measurement of images obtained at ERCP, even when corrections are made for radiographic magnification.
