ABSTRACT
Insulin/IGF signaling in Caenorhabditis elegans is crucial for proper development of the dauer larva and growth control. Mutants disturbing insulin processing, secretion and downstream signaling perturb this process and have helped identify genes that affect progression of type 2 diabetes. Insulin maturation is required for its proper secretion by pancreatic ß cells. The role of the endoplasmic reticulum (ER) chaperones in insulin processing and secretion needs further study. We show that the C. elegans ER chaperone ENPL-1/GRP94 (HSP90B1), acts in dauer development by promoting insulin secretion and signaling. Processing of a proinsulin likely involves binding between the two proteins via a specific domain. We show that, in enpl-1 mutants, an unprocessed insulin exits the ER lumen and is found in dense core vesicles, but is not secreted. The high ER stress in enpl-1 mutants does not cause the secretion defect. Importantly, increased ENPL-1 levels result in increased secretion. Taken together, our work indicates that ENPL-1 operates at the level of insulin availability and is an essential modulator of insulin processing and secretion.
Subject(s)
Caenorhabditis elegans Proteins/metabolism , HSP70 Heat-Shock Proteins/chemistry , Insulin Secretion , Membrane Proteins/chemistry , Molecular Chaperones/metabolism , Proinsulin/metabolism , Protein Processing, Post-Translational , Sequence Homology, Amino Acid , Amino Acid Sequence , Animals , Caenorhabditis elegans/embryology , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/chemistry , Cell Compartmentation , Conserved Sequence , Embryo, Nonmammalian/metabolism , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress , Green Fluorescent Proteins/metabolism , Molecular Chaperones/chemistry , Mutation/genetics , Neurons/metabolism , Protein Domains , Protein Transport , Secretory VesiclesABSTRACT
Skeletal muscle metastasis as the initial presentation of the unknown primary lung cancer is unusual. A 65-year-old male patient presented with pain and swelling of the right forearm. Fine needle aspiration of the swelling revealed metastatic squamous cell carcinoma. The patient underwent whole body F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to identify the site of the primary malignancy. The authors present PET/CT images showing FDG-avid metastases to the skeletal muscles along with a previously unknown primary tumor in the right lung, in a patient presenting with initial muscular symptoms without any pulmonary manifestations.
ABSTRACT
Cisplatin is an essential chemotherapeutic drug in the treatment of many cancers. Its use, however, is limited by the development of resistance in many tumors. The ability to re-sensitize resistant tumors could significantly strengthen cisplatin therapy in patients. Caenorhabditis elegans is a suitable model for studying the cytoplasmic role of cisplatin in tumor cells. We have previously shown that the ATPase ASNA-1 has similar roles as a factor governing cisplatin sensitivity in mammalian tumor cells and C. elegans. Here we study the endoplasmic reticulum (ER) resident chaperone ENPL-1/GRP94 and find that its depletion makes worms sensitive to cisplatin. Elevated ER stress levels in enpl-1 mutants is the likely cause of this sensitivity because a correlation can be made between cisplatin sensitivity and the high ER stress levels. We also find that asna-1 mutants have elevated unfolded protein response (UPR) activity and that the intrinsically cisplatin resistant wild-type worms become sensitive when ER stress is high. We conclude that enpl-1 is a cisplatin sensitizing factor and suggest that manipulation of its levels or of UPR activity will enhance the effects of cisplatin based cancer therapy.
ABSTRACT
Autoimmune pancreatitis and pancreatic cancer share many clinical features like advanced age, painless jaundice, weight loss, and elevated serum levels of CA 19-9. The authors report a 58-year-old male patient provisionally diagnosed with periampullary carcinoma on the basis of ultrasonography and serological markers and planned for Whipple resection. (18)F-FDG PET/CT findings were suggestive of autoimmune pancreatitis, subsequently confirmed on cytological diagnosis. The follow-up PET/CT scan after 1 week of steroid therapy showed regression of FDG uptake in most of the lesions with appearance of salivary gland uptake.
Subject(s)
Autoimmune Diseases/diagnostic imaging , Fluorodeoxyglucose F18 , Pancreatitis/diagnostic imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Autoimmune Diseases/drug therapy , Humans , Male , Middle Aged , Pancreatitis/drug therapyABSTRACT
Metastatic tumors of the penis are rare, with priapism as the predominant symptom in a significant number of cases. The genitourinary tract and rectum are the most common primary sites. FDG PET/CT has established role in detection of distant metastasis in various malignancies. The authors describe a case of mucoid adenocarcinoma of cecum, presented with priapism after right hemicolectomy, where FDG PET/CT showed intense tracer uptake throughout the enlarged penis, which was later confirmed as metastatic adenocarcinoma by trucut biopsy.
Subject(s)
Adenocarcinoma, Mucinous/secondary , Cecum/diagnostic imaging , Fluorodeoxyglucose F18 , Intestinal Neoplasms/secondary , Multimodal Imaging , Penile Neoplasms/pathology , Positron-Emission Tomography , Priapism/complications , Tomography, X-Ray Computed , Adenocarcinoma, Mucinous/diagnostic imaging , Humans , Intestinal Neoplasms/diagnostic imaging , Male , Middle Aged , Penile Neoplasms/complicationsABSTRACT
Diffuse infiltration by a primary or metastatic malignancy into the submucosa and muscularis of the stomach (linitis plastica [LP]) has been described in literature. The authors present a case of LP caused by primary adenocarcinoma of the stomach, showing diffuse Fluorine-18 fluorodeoxyglucose uptake in the thickened wall of the stomach.
ABSTRACT
Genes regulating Caenorhabditis elegans insulin/IGF signaling (IIS) have largely been identified on the basis of their involvement in dauer development or longevity. A third IIS phenotype is the first larval stage (L1) diapause, which is also influenced by asna-1, a regulator of DAF-28/insulin secretion. We reasoned that new regulators of IIS strength might be identified in screens based on the L1 diapause and the asna-1 phenotype. Eighty- six genes were selected for analysis by virtue of their predicted interaction with ASNA-1 and screened for asna-1-like larval arrest. ykt-6, mrps-2, mrps-10 and mrpl-43 were identified as genes which, when inactivated, caused larval arrest without any associated feeding defects. Several tests indicated that IIS strength was weaker and that insulin secretion was defective in these animals. This study highlights the role of the Golgi network and the mitochondria in insulin secretion and provides a new list of genes that modulate IIS in C. elegans.
Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/metabolism , Insulin/metabolism , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/growth & development , Caenorhabditis elegans Proteins/physiology , Insulin Secretion , Larva/growth & development , Mitochondria/metabolism , Mitochondria/physiology , RNA Interference , Signal Transduction/genetics , Somatomedins/genetics , Somatomedins/metabolism , Somatomedins/physiologySubject(s)
Adenocarcinoma, Papillary/diagnostic imaging , Adenocarcinoma, Papillary/secondary , Fluorine Radioisotopes , Ovarian Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/secondary , Adenocarcinoma, Papillary/metabolism , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Female , Fluorine Radioisotopes/pharmacokinetics , Humans , Middle Aged , Ovarian Neoplasms/metabolism , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Soft Tissue Neoplasms/metabolismABSTRACT
Polyostotic fibrous dysplasia is a rare progressive benign disorder of the bone. Bone scintigraphy is extremely useful in the initial evaluation for identifying the extent of disease. We report a case presenting with pathological fracture of the shaft of the right femur. After treatment of the fracture, bone scintigraphy revealed involvement of multiple bones including the skull and facial bones. The utility of single-photon emission computed tomography/computerized tomography in the evaluation of the extent of skull base involvement is highlighted.
Subject(s)
Fluorides , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Forearm/diagnostic imaging , Multimodal Imaging , Myositis Ossificans/diagnostic imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Female , Fluorides/metabolism , Fluorodeoxyglucose F18/metabolism , Humans , Myositis Ossificans/metabolism , Myositis Ossificans/pathology , Myositis Ossificans/physiopathology , Young AdultABSTRACT
The present study investigates the potential use of activated carbon prepared from Cassia tora by sulphuric acid treatment for the removal of Chromium(VI) from aqueous solution. The effects of pH, initial concentration, contact time, and carbon concentration were studied for the sorption of Cr(VI) in batch mode. The optimum pH value for Cr(VI) adsorption was determined as 2.0. The experimental results were fitted with the Freundlich, Langmuir and Redlich Peterson equations to describe the equilibrium isotherms. The Langmuir and Redlich - Peterson isotherm models were found better to describe the experimental data. The maximum adsorption capacity obtained from Langmuir equation was 72.4 mg/g. The kinetic data were then fitted with the Lagergren-first-order, pseudo-second-order and intraparticle models. Further, adsorption kinetics of Cr(VI) was studied and the rate of adsorption was found to confirm pseudo-second-order kinetics with a good correlation and intraparticle diffusion as one of the rate determining steps. Activated carbon developed from Cassia tora can be a potential alternative for Cr(VI) removal from aqueous solution.
