Cell and Developmental Biology Commons^™

Immunohistochemical Evaluation Of Small Round Cell Tumors Of Childhood, Sajid H. Shah, Irshad N. Soomro, M. Shahid Siddiqui, Shahid Pervez, Sheema H. Hassan

Department of Pathology and Laboratory Medicine

Objective:

This study was done to evaluate the pediatric undifferentiated small round cell tumors with immunohistochemical staining.

Setting:

The present study included consecutive cases of small round cell tumors which were diagnosed in children (<15 years) in the section of Histopathology at the Aga Khan University Hospital, Karachi during the period of two years.

Methods:

The group of undifferentiated small round cell tumors were evaluated immunohistochemically by using a panel of antibodies on sections from routinely processed, formalin fixed, paraffin embedded tissue blocks.

Results:

The category of undifferentiated small round cell tumors included rhabdomyosarcoma (23.2%), primitive neuroectodermal tumor (17.9%), non-Hodgkin’s lymphoma (16.1%), neuroblastoma (14.2%), Ewing’s sarcoma (10.7%) in order of frequency. Osteosarcoma (Small cell variant), retinoblastoma and medulloblastoma comprised …

Reaction-Diffusion Models Of Cancer Dispersion, Kim Yvette Ward

Mathematics & Statistics Theses & Dissertations

The phenomenological modeling of the spatial distribution and temporal evolution of one-dimensional models of cancer dispersion are studied. The models discussed pertain primarily to the transition of a tumor from an initial neoplasm to the dormant avascular state, i.e. just prior to the vascular state, whenever that may occur. Initiating the study is the mathematical analysis of a reaction-diffusion model describing the interaction between cancer cells, normal cells and growth inhibitor. The model leads to several predictions, some of which are supported by experimental data and clinical observations $\lbrack25\rbrack$. We will examine the effects of additional terms on these characteristics. …

Interleukin-2 Fusion Protein: An Investigational Therapy For Interleukin-2 Receptor Expressing Malignancies, Jean Nichols, Foss Francine, Kuzel Timothy, Lemaistre Charles Fred, Platanias Leonidas, Ratain Mark, Rook Alain, Mansoor Saleh, Schwartz Gary

Haematology and Oncology, East Africa

DAB3s91L-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a molecular weight of 58 kD containing the enzymatic and translocation domains of diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the cytocidal action of the DT enzymatic region only to cells which bear the IL-2R. The human IL-2R exists in three forms: low, intermediate and high affinity. The high-affinity form is believed to be the biologically relevant form on mature, activated T-lymphocytes, B-lymphocytes and monocytes. DAB3sgIL-2 is able to bind selectively to the high-affinity IL-2R in a concentration-dependent manner, and once bound is internalised …

Phase Ia/Ib Trial Of Anti-Gd2 Chimeric Monoclonal Antibody 14.18 (Ch L4.18) And Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (Rhgm-Csf) In Metastatic Melanoma, James Murray, Eugenie Kleinerman, Shu-Fang Jia, Michael Rosenblum, Omar Eton, Antonio Buzaid, Sewa Legha, Merrick Ross, Lora Thompson, Mansoor Saleh

Haematology and Oncology, East Africa

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral …

Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom

Haematology and Oncology, East Africa

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a …

Cd16+ Monocytes In Patients With Cancer: Spontaneous Elevation And Pharmacologic Induction By Recombinant Human Macrophage Colony- Stimulating Factor, Mansoor Saleh, Goldman Samuel, Lobuglio Albert, Beall Arthur, Sabio Hernan, Mccord Melissa, Minasian Lori, Alpaugh Katherine, Weiner Louis, Munn David

Haematology and Oncology, East Africa

The small subset of circulating monocytes that express the maturation- associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled in a clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill …

The Role Of Small Peptides In Cancer Physiology And Chemotherapy, Bao-Ling Tsay

Theses and Dissertations in Biomedical Sciences

The targeting of proven anticancer drugs specifically to cancer cells would provide a unique opportunity to restrict neoplasms without damaging the cancer patient. The present research utilizes the phenomenon of illicit transport, i.e. the coupling of normally impermeant metabolites to permeant metabolites, in targeting the drug melphalan to mouse Ehrlich ascites tumor cells. The dipeptide beta-alanyl-melphalan was synthesized and tested in vitro for toxicity towards mouse Ehrlich ascites tumor cells, mouse liver cells, and mouse 3T3 embryonic cells. The parent compound, melphalan, was used as a control treatment. In addition, both melphalan and beta-alanyl-melphalan were utilized in in vivo chemotherapeutic …

Hypoxanthine-Induced Differentiation Of Cultured Human Leukemia Cells, Gayle Jennette Singleton

Chemistry & Biochemistry Theses & Dissertations

Human cultured leukemia cells appear to have a decreased amount of inosine in their tRNA. When cells with inosine deficient tRNA are placed in a hypoxanthine fortified media, they incorporate hypoxanthine into their tRNA by the action of the enzyme tRNA-hypoxanthine ribosyl transferase. This generates the nucleoside inosine in the tRNA. The cultured human leukemia cell lines, CCRF-CEM, HL-60, and HGPRT(-) HL- 60, incorporate hypoxanthine into their tRNA, as determined by tRNA isolation, hydrolysis, and HPLC analysis. Hypoxanthine treatment dramatically inhibited cell growth in conjunction with partial induction of differentiation in the CCRF-CEM, HL-60, and HGPRT ( - ) HL-60 …

Effect Of Intravenous Gammaglobulin On Circulating And Platelet-Bound Antibody In Immune Thrombocytopenia, G Garbano, Mansoor Saleh, P G. Mori, A F. Lobuglio, D Shaw

Haematology and Oncology, East Africa

Ten patients with idiopathic thrombocytopenic purpura (ITP) were studied before and following a rise in circulating platelets subsequent to infusions of intravenous gammaglobulin (400 mg/kg/day x 5 days). We quantitated the amount of circulating IgG capable of binding to normal donor platelets in vitro using an 125I-monoclonal anti-human IgG assay, as well as the amount of IgG associated with the patients' platelets before and following therapy. We found no evidence for a decrease in platelet-specific IgG antibodies in these patients undergoing an acute response to therapy. These data suggest that the short-term efficacy of intravenous gammaglobulin is due to effects …

Clinical Use Of A Standard Kit-Preparation Of Radiolabeled Monoclonal Antibody 96.5 In The Diagnostic Imaging Of Metastatic Melanoma., Mansoor Saleh, D M. Miller, L Peterson, C D. Russell, M W. Unger

Haematology and Oncology, East Africa

We studied the efficiency of a standard-kit preparation using 1 mg 111In-labeled 96.5 monoclonal antibody in combination with 19 mg of unlabeled antibody in the diagnostic imaging of 27 patients with documented metastatic melanoma. Twenty-three of 26 patients (88%) demonstrated immunoscintigraphic localization of tumor. Of 104 metastatic sites previously documented by conventional studies, 62 (60%) were identified by immunoscintigraphy. A total of 77 sites demonstrated localization of radiolabeled antibody. Fifty-four (70%) corresponded to known sites of disease; eight sites (10%) were "discovered" by immunoscintigraphy and subsequently confirmed by conventional studies; 15 imaged sites (20%) could not be confirmed by conventional …

The Analysis Of S-Adenosylmethionine And S-Adenosylhomocysteine In Normal And Neoplastic Cells, Kathryn Elizabeth Godburn

Chemistry & Biochemistry Theses & Dissertations

Altered patterns of methylation have been shown in both ribosomal and transfer RNA isolated from cancer cells. In contrast to the elevated activity of the methyltransferases responsible for this modification, hypomethylation appears as a general characteristic. The endogenous levels of S-adenosylmethionine and S-adenosylhomocysteine are important in relationship to their role as substrate and product of the transmethylation reaction. The levels of S-adenosylmethionine and S-adenosylhomocysteine were determined using phosphocellulose cation exchange or high pressure liquid chromatography. High voltage paper electrophoresis was used in a modified procedure to directly resolve (³⁵s) labeled S-adenosylmethionine and S-adenosylhomocysteine in small quantities of cell …

Detection Of Unique Tumor-Associated Proteins In The Urine Of Patients With Transitional Cell Carcinoma By High Resolution Two-Dimensional Polyacrylamide Gel Electrophoresis, Robert David Lehman

Biological Sciences Theses & Dissertations

A two-dimensional polyacrylamide gel electrophoretic technique was developed for the detection of unique tumor-associated proteins in urine of patients with transitional cell carcinoma (TCC) of the urinary bladder. This technique yielded high resolution of polypeptides in the urine of cancer patients. Urine was chosen as a source of tumor-associated components because the location of the tum or should release already solublized tum or substances in to the urine.

Urinary proteins were concentrated and then analyzed by the two - dimensional electrophoretic technique using isoelectric focusing in the first dimension and sodium dodecylsulfate - polyacrylamide gel electrophoresis in the second dimension. …