ABSTRACT
We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.
Subject(s)
Hyperglycemic Hyperosmolar Nonketotic Coma/chemically induced , Induction Chemotherapy/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Fluid Therapy/methods , Humans , Hyperglycemic Hyperosmolar Nonketotic Coma/diagnosis , Hyperglycemic Hyperosmolar Nonketotic Coma/therapy , Induction Chemotherapy/methods , Insulin/therapeutic use , MaleABSTRACT
Prostate cancer is a major cause of death in older men, and bone metastasis is the primary cause of morbidity and mortality in prostate cancer. Prostate is an abundant source of nerve growth factor (NGF) that is secreted by malignant epithelial cells and utilized as an important autocrine factor for growth and metastasis. We previously showed that intravenous gammaglobulin (IVIg) contains natural antibodies against NGF, which inhibit growth and differentiation of the NGF-dependent cell line PC-12. In the present study, we examined the effects of these natural antibodies on in vitro migration or metastasis of two prostate cancer cell lines namely DU-145 and PC-3. Cancer cell migration was assessed using these cell lines in the upper chambers of Matrigel invasion chambers. The effects of IVIg and affinity-purified anti-NGF antibodies on cell migration through membrane into the lower chamber were assessed in dose/response experiments by a colorimetric method. Affinity-purified natural IgG anti-NGF antibody inhibited DU-145 migration by 38% (p = 0.01) and PC-3 migration by 25% (p = 0.02); whereas, a monoclonal anti-NGF antibody inhibited DU-145 migration by 40% (p = 0.01) and PC-3 migration by 37% (p = 0.02), at the same concentration. When IVIg was depleted of NGF-specific IgG by affinity chromatography, there was no significant inhibition of migration of the DU-145 and PC-3 cells at a concentration of 1 mg/well. Removal of the NGF-specific antibody from the IVIg was also demonstrated by a lack of effect on PC-12 cell differentiation. Therefore, IVIg is able to inhibit the migration of prostate cancer cell lines, through Matrigel chambers in vitro, only when the natural NGF-specific antibodies actively are present in IVIg.
Subject(s)
Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/pharmacology , Nerve Growth Factor/antagonists & inhibitors , Prostatic Neoplasms/pathology , Cell Movement/drug effects , Dose-Response Relationship, Drug , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Neoplasm Metastasis/drug therapy , Neoplasm Metastasis/immunology , Neoplasm Metastasis/pathology , Nerve Growth Factor/immunology , Prostatic Neoplasms/immunology , Prostatic Neoplasms/therapy , Tumor Cells, CulturedABSTRACT
Neurotrophins are regulators of development, survival and function of neuronal and non-neuronal cells, one of the most important of which is nerve growth factor (NGF). Previous studies have demonstrated the presence of antibodies to NGF in normal human serum. It would therefore be predicted that antibodies to NGF would also be present in commercial intravenous gammaglobulin (IVIg). It has been shown in the present investigation that ELISA can detect anti-NGF antibodies in IVIg. The functional activity of these antibodies has been demonstrated after affinity purification, by their inhibitory effects upon (a) the proliferation of the NGF-responsive rat pheochromocytoma cell line PC-12, (b) the differentiation of PC-12 cells as determined by neurite outgrowth. All batches of commercially tested IVIg contained anti-NGF antibodies. Since NGF has an important role in the inflammatory immune response and in cell growth and differentiation, these findings may (a) facilitate our understanding of the mechanisms of action of IVIg, (b) indicate new disease states in which IVIg or its derivatives may exert beneficial effects.
