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Biomedical subjects

A J Murgo

Publications and source records attributed to A J Murgo.

At least 19 recordsLinked to original sources
PubMed2001

Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies.

Arsenic trioxide inhibits growth and promotes apoptosis in many different cancer cell lines. The National Cancer Institute is working cooperatively with research centers across the U.S. to evaluate its clinical activity in hematologic malignancies, such as acute promyelocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myelodysplastic syndrome, and multiple myeloma. It is also supporting research in solid tumors, such as advanced hormone-refractory prostate cancer and renal cell cancer and in cervical cancer and refractory transitional cell carcinoma of the bladder. The safety and pharmacokinetics of arsenic trioxide are also being evaluated in pediatric patients with refractory leukemia and lymphoma. The results of these ongoing studies should provide important insights into the clinical utility of arsenic trioxide in these diseases.

Antineoplastic Agents↗
PubMed1997

Methionine enkephalin: a new cytokine--human studies.

The effects of methionine enkephalin (met-enkephalin) on human immune function are reviewed. This pentapeptide functions to upregulate, or enhance, immune function in the majority of donor samples at low doses and suppresses at high doses. The influence of this molecule is shared by the central nervous, neuroendocrine, and immune systems. Cells from each of these systems possess receptors for met-enkephalin and have the ability to process met-enkephalin from its prohormone, proenkephalin A. Studies have shown that this molecule is capable of enhancing immune function in patients with cancer or AIDS. It is proposed that this molecule be classified as a cytokine.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Promising new agents under development by the Division of Cancer Treatment, Diagnosis, and Centers of the National Cancer Institute.

The Division of Cancer Treatment, Diagnosis and Centers of the National Cancer Institute (NCI) has a large program in clinical cancer therapeutics development. It currently holds investigational new drug applications for nearly 200 agents with which it sponsors clinical trials. In addition, it has a major preclinical development program. With the tremendous advances in our understanding of molecular and tumor biology during the past decade, the NCI's portfolio of agents has expanded beyond classical cytotoxic agents to include a wide variety of new molecular and therapeutic targets. In addition to agents with more conventional mechanisms of action, the NCI has targeted therapeutics programs that focus on tumor vasculature, cell cycle control and cell signaling, mechanisms of apoptosis, invasion and metastasis, and immunological recognition and response. Each of these focused areas includes agents of different classes and modes of action that are all directed at the target of interest. The scope of the NCI's program allows it to respond to incorporate promising new agents or targets as they arise and to prioritize them for use of preclinical and clinical resources. Agents in development through the NCI are derived from a number of diverse sources including its own screening efforts, academia, and numerous collaborations with the pharmaceutical and biotechnology industries. NCI works closely with collaborators to ensure complementary, non-duplicative clinical development and attempts to ensure that the full potential of promising agents is explored. A number of compounds in early clinical development or about to enter the clinic are discussed briefly in this manuscript.

Antineoplastic Agents↗
PubMed1994

Evidence for separate calcium-signaling P2T and P2U purinoceptors in human megakaryocytic Dami cells.

Recently (J Pharmacol Exp Ther 261:580, 1992), we have shown that K562 leukemia cells express a calcium-signaling purinoceptor with characteristics of the P2T receptor subtype for adenosine diphosphate (ADP) previously found only in platelets. Because these results suggested that the P2T receptor may be an early marker for megakaryocytic differentiation, we studied whether this calcium-signaling receptor is also expressed in Dami cells, a human megakaryocytic leukemia cell line. Here we report evidence that Dami cells express a P2T receptor for ADP. The calcium response EC50 values for ADP, 2-methylthioadenosine diphosphate (2-MeS-ADP), and adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) in Dami cells are 0.4 mumol/L, 0.04 mumol/L, and 2 mumol/L, respectively, which approximate the potencies of these agonists in K562 cells and in platelets. The platelet P2T receptor antagonists 2-methylthioadenosine triphosphate (2-MeS-ATP), and 2-chloroadenosine triphosphate (2-Cl-ATP) were surprisingly potent agonists at the P2T receptor in both Dami and K562 cells. Dami cells, unlike K562 cells and platelets, also respond to adenosine triphosphate (ATP) and uridine triphosphate (UTP) with an increase in intracellular calcium. Adenosine monophosphate (AMP) is an effective antagonist of the response to ADP, 2-MeS-ADP, ADP beta S, 2-MeS-ATP, and 2-Cl-ATP, but not to ATP and UTP. The responses to maximal concentrations of UTP in combination with either ADP, 2-MeS-ADP, ADP beta S, or 2-MeS-ATP are additive. In contrast, ADP in combination with either 2-MeS-ADP, ADP beta S, 2-MeS-ATP, or 2-Cl-ATP are not additive. UTP desensitized Dami cells to ATP but not to ADP, 2-MeS-ADP, ADP beta S, or 2-MeS-ATP. Addition of ATP after UTP desensitization antagonized subsequent responsiveness to ADP. The data suggest that the receptor for ADP may be a unique P2T subtype, and the receptor for ATP and UTP is distinct from that of ADP and is most characteristic of the P2U (nucleotide) receptor subtype. Activation of either the P2T or P2U receptor causes a rapid generation of inositol trisphosphate in Dami cells.

Adenine Nucleotides↗
PubMed1992

K562 leukemia cells express P2T (adenosine diphosphate) purinergic receptors.

The P2T purinergic receptor for ADP has previously been found only in platelets. We investigated the effect of ADP on the concentration of intracellular free calcium ([Ca++]i) in fura-2-loaded K562 leukemia cells, a cell line with the potential for megakaryocytic differentiation. ADP causes a rapid and transient increase in [Ca++]i, which peaks within 5 to 10 sec. The EC50 for this response is 0.4 microM. A major portion of the increased calcium is due to mobilization of intracellular stores because the response to ADP is only partially reduced in the absence of extracellular calcium. Exposure to ADP desensitizes K562 cells to additional administrations of this nucleotide. Pretreatment of K562 cells with the protein kinase C activator phorbol 12-myristate 13-acetate completely blocks the response to ADP. This effect of phorbol 12-myristate 13-acetate is prevented by the protein kinase C inhibitor staurosporine, but staurosporine does not affect the progression of desensitization after repeated ADP exposures. ATP does not increase [Ca++]i in K562 cells, but antagonizes the response to ADP. We propose that the P2T receptor for ADP in K562 cells is an early marker for megakaryocytic differentiation. Furthermore, this immortalized nucleated cell line may be a useful model to decipher the signal transduction pathways involved in the ADP response.

Adenosine Diphosphate↗
PubMed1991

The role of the FDA in new drug development and availability.

During the last decade, the process by which the FDA regulates investigational new drugs has become a renewed focus of national attention. The ability of the FDA to maintain a balance between accelerating the availability of new drugs and ensuring that patients do not receive unsafe or ineffective treatments has been particularly challenged by the AIDS crisis. In response to this crisis, the FDA has revised its regulations and created various formal mechanisms for expediting the development and accessibility of promising new therapies to treat AIDS and other serious illnesses. Regulatory requirements have been reduced and consultation with the FDA to discuss the planning and design of clinical research is encouraged.

Drug Industry↗
PubMed1990

Effects of stress on the immune system.

Stress, distress and a variety of psychiatric illnesses, notably the affective disorders, are increasingly reported to be associated with immunosuppression. The concept that psychic distress may predispose to medical illness is centuries old but has only recently attracted the attention of the scientific community at large. Interdisciplinary collaboration has established psychoneuroimmunology, or neuroimmunomodulation, as a new field of investigation with the goal of rigorous scientific research into the elusive mind-body connection. This has resulted in the rapid accumulation of information which falls across the boundary lines of psychiatry, immunology, neurosciences and endocrinology. Here David Khansari, Anthony Murgo and Robert Faith review the effects of stress on the endocrine and central nervous systems and the interactions between these systems and the immune response after exposure to stress signals.

Animals↗
PubMed1989

Modulation of murine melanoma growth by naloxone.

The present study was undertaken to determine the effect of the opioid receptor antagonist, naloxone, on the growth of B16 melanoma, a murine tumor known to possess opioid receptors. Naloxone inhibited the growth of B16 melanoma in vitro when monolayer cultures were continuously exposed to concentrations of greater than or equal to 0.25 mg/ml. Tumor cell proliferation as measured by [3H]thymidine ([3H]Tdr) incorporation is reduced by a continuous 48-h treatment with greater than or equal to 0.025 mg/ml but slightly enhanced by a 6-h treatment. The administration of naloxone to mice caused a transient inhibition of subcutaneous local tumor growth at doses of 0.1, 1 and 10 mg/kg daily. At a dose of 10 mg/kg daily, naloxone caused a slight reduction in the number of pulmonary metastases following the intravenous inoculation of tumor cells. The mechanism by which naloxone inhibits tumor growth in vivo is not clear, but factors other than direct cytotoxicity may also be involved. The results further support the role of the endogenous opioid system in the modulation of tumor growth.

Animals↗
PubMed1989

Immunological approaches to cancer treatment.

A better understanding of cellular immunology and advances in recombinant DNA technology have led to a new dimension in the immunological treatment of cancer in which the potential for success is greatly increased. The number of biological agents with the ability to enhance the host's anti-tumor defense mechanisms has markedly increased during the last decade. The development of clinical trials with these biological response modifiers is an area of intense research. As a result of these investigations, a variety of malignancies now can be treated successfully by immunological approaches.

Humans↗
PubMed1988

Inhibition of pulmonary metastases and enhancement of natural killer cell activity by methionine-enkephalin.

Studies were performed to investigate the effects of the endogenous opioid peptide methionine enkephalin on experimental metastasis of the murine B-16 melanoma and on murine splenic natural killer cell activity. Methionine enkephalin was shown to significantly inhibit tumor metastasis and significantly enhance splenic natural killer cell activity. These results indicate that the endogenous opioids can modulate the immune response and tumor defense and that methionine-enkephalin may prove to be a beneficial adjunct to the therapy of neoplastic disease.

Animals↗
PubMed1988

Chemotherapy for breast cancer decreases plasma protein C and protein S.

An increased incidence of thromboembolic events has been described in women receiving chemotherapy for breast cancer. The etiology of this enhanced thrombotic state has not been defined. We performed serial coagulation studies in 15 women during 1 monthly cycle of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer; seven adjuvant and eight metastatic. Plasma protein C levels were measured by anticoagulant, amidolytic, and antigenic techniques. Antigen levels of both total and free plasma protein S were quantitated by immunoelectrophoresis. Plasma levels of protein C, an important vitamin K-dependent inhibitor of blood coagulation and a profibrinolytic agent, and protein S, a cofactor for protein C, decreased 1 and 2 weeks after initiation of chemotherapy compared with pretreatment values. Plasma levels of factor VII and fibrinogen also decreased. The changes in protein C and protein S may contribute to the enhanced thrombotic tendency described in this setting. Possible mechanisms for the decreases in plasma protein C, protein S, factor VII, and fibrinogen are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Enhancement of host resistance to viral and tumor challenge by treatment with methionine-enkephalin.

Host resistance to disease is dependent upon a number of factors. Recent evidence indicates that natural killer (NK) cells play an important role in resistance to both neoplastic and virally induced disease. Treatment of C57Bl/6 mice with methionine-enkephalin (1, 3, 10, or 30 mg/kg body weight) results in significant increases in NK activity of splenic lymphocytes 20 hours after injection of the enkephalin. Enkephalin treatment also enhances host resistance. The short-term survival of A/J female mice after HSV-2 infection was significantly increased by daily subcutaneous injections (3 mg/kg body weight) of methionine-enkephalin. Similarly, daily doses of 50 micrograms of methionine-enkephalin for 7 to 14 days inhibit the local subcutaneous tumor growth of B15 melanoma in C57Bl/6 mice.

Adjuvants, Immunologic↗