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1.
Oncogene ; 36(21): 3025-3036, 2017 05 25.
Article in English | MEDLINE | ID: mdl-27941884

ABSTRACT

Epithelial ovarian carcinoma is the most common cause of death from gynecologic cancers largely due to advanced, relapsed and chemotherapy-resistant peritoneal metastasis, which is refractory to the currently used treatment approaches. Mechanisms supporting advanced and relapsed peritoneal metastasis are largely unknown, precluding development of more effective targeted therapies. In this study, we investigated the function of a potentially targetable fractalkine axis in the formation and the development of advanced and relapsed peritoneal metastasis and its impact on patients' outcomes. Our mouse model studies support a role for the fractalkine receptor (CX3CR1) in the initiation of peritoneal adhesion important for recolonization of relapsed peritoneal metastasis. We show that downregulation of CX3CR1 results in reduction of metastatic burden at several peritoneal sites commonly colonized by advanced and relapsed metastatic ovarian carcinoma. We show that the chemokine fractalkine (CX3CL1), an activating ligand of CX3CR1, regulates organ-specific peritoneal colonization. High expression of CX3CR1 correlates with significantly shorter survival, specifically in post-menopausal patients with advanced and terminal stages of the disease. Taken together, our studies support a key regulatory role for the fractalkine axis in advanced and relapsed peritoneal metastasis in epithelial ovarian carcinoma.


Subject(s)
Chemokine CX3CL1/physiology , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/secondary , Receptors, Chemokine/physiology , Animals , CX3C Chemokine Receptor 1 , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Chemokine CX3CL1/genetics , Female , Humans , Mice , Mice, Inbred C57BL , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Receptors, Chemokine/genetics , Signal Transduction/genetics , Survival Analysis
2.
World J Urol ; 16(6): 413-6, 1998.
Article in English | MEDLINE | ID: mdl-9870291

ABSTRACT

Hyperoxaluria was reported to induce renal damage, probably due to toxic effects on renal tubules. Such tubular damage might be expressed by an increase in urinary excretion of marker enzymes such as N-acetyl-beta-D-glucosaminidase (NAG). We set out to examine a possible relationship between the excretion of NAG and that of urinary lithogenic and stone-inhibitory substances by analyzing 24-h urine specimens from 56 children with urolithiasis and 25 healthy children with normal renal function and without a history of urolithiasis. The NAG excretion was higher in patients with urolithiasis (3.5 +/- 0.51 U/g creatinine) as compared with healthy subjects (1.33 +/- 0.14 U/g creatinine, P < 0.05). A positive correlation between NAG and oxalate excretion was observed in female patients (r = 0.56: P < 0.01). In conclusion, the increase in urinary NAG in children with urolithiasis might express renal tubular damage. It seemed, however, not to be specifically related to the excretion of a single lithogenic substance.


Subject(s)
Acetylglucosaminidase/urine , Urinary Calculi/enzymology , Adolescent , Biomarkers/urine , Calcium/urine , Child , Child, Preschool , Citric Acid/urine , Creatinine/urine , Female , Follow-Up Studies , Humans , Hyperoxaluria/complications , Hyperoxaluria/enzymology , Hyperoxaluria/urine , Kidney Tubules/metabolism , Magnesium/urine , Male , Oxalates/urine , Phosphates/urine , Photometry , Urinary Calculi/etiology , Urinary Calculi/urine
3.
Urol Int ; 61(3): 154-6, 1998.
Article in English | MEDLINE | ID: mdl-9933835

ABSTRACT

Urolithiasis is a very frequent finding in the Sudan, but stone analysis is not routinely performed in this country. It would, however, give important evidence for the metabolic basis of stone formation. We therefore set out to analyze urinary stones in 80 Sudanese patients (45 male, 35 female), 12 of whom where children. Fourier-transformed infrared spectroscopy was used for stone analysis. As is known from other countries, calcium oxalate (CaOx) stones were the most frequent, with 68.7% of all stones in adults and 43.7% of childhood stones. Uric acid and uric acid dihydrate stones were more often seen in adults (13.2%) than in children (4. 1%). Ammonium urate stones are common in the Sudan, especially in children (32.9%), which is typical for underdeveloped countries. Infectious stones (struvite and carbonate apatite) were more often found in women (7.0%) and in children (5.3%) than in men (1.4%). Brushite stones were seldom seen and cystine stones did not occur.


Subject(s)
Kidney Calculi/chemistry , Adolescent , Adult , Calcium Oxalate/chemistry , Child , Child, Preschool , Female , Humans , Incidence , Kidney Calculi/epidemiology , Male , Middle Aged , Oxalates/chemistry , Spectrophotometry , Sudan/epidemiology , Uric Acid/chemistry
4.
Radiographics ; 17(6): 1387-402, 1997.
Article in English | MEDLINE | ID: mdl-9397453

ABSTRACT

Hyaline cartilage plays an essential role in the maintenance of normal synovial joint function by reducing friction and distributing loads. Histologic analysis of hyaline cartilage reveals zonal variation in cellular morphology, proteoglycan concentration, and collagen fiber size and orientation. High-resolution magnetic resonance (MR) imaging reveals an analogous laminar anatomy that is often visible on clinical images obtained with proper attention to technique. In vitro and in vivo pulse sequences show three distinct laminae: a hypointense superficial lamina, a hyperintense intermediate lamina, and a heterogeneous deep lamina that consists of alternating hyperintense and hypointense bands perpendicular to the subchondral bone. Imaging pitfalls include magic angle effects, truncation artifact, partial volume effect, regional anatomic variation, chemical shift, and magnetic susceptibility effects. Pathologic conditions that affect articular cartilage include chondromalacia patellae, osteoarthritis, and localized traumatic lesions. Although detection of early cartilage disease remains elusive, MR imaging can demonstrate intermediate and advanced lesions.


Subject(s)
Cartilage, Articular/pathology , Hyalin/ultrastructure , Magnetic Resonance Imaging , Adult , Artifacts , Collagen/ultrastructure , Female , Humans , Image Enhancement , Image Processing, Computer-Assisted , Knee Joint/pathology , Male , Middle Aged , Osteochondritis/pathology , Reference Values
8.
J Immunol Methods ; 9(3-4): 205-9, 1976.
Article in English | MEDLINE | ID: mdl-1082460

ABSTRACT

Sera from five animal species were studied as complement source in the preparation of zymosan-C3 complexes used to detect human B lymphocytes. There was no significant difference in the determination of the percentage of ZC rosette forming cells due to differences in complement source. Human B lymphocytes could not discriminate C3 from different species studied. Every one of these sources of complement may be used interchangeably without altering the percentage of B cells detected by this method.


Subject(s)
B-Lymphocytes , Complement C3/metabolism , Complement System Proteins/metabolism , Immune Adherence Reaction , Zymosan/metabolism , Adolescent , Adult , Animals , Blood Cell Count , Female , Guinea Pigs , Humans , Male , Mice , Middle Aged , Rabbits , Sheep
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