Differential metabolism of deoxyribonucleosides by leukaemic T cells of immature and mature phenotype

Experimental evidence has indicated that T lymphoblasts are more sensitive to deoxynucleoside toxicity than are B lymphoblasts. These data have led to the use of purine enzyme inhibitors as selective chemotherapeutic drugs in the treatment of T cell malignancies ranging from T cell acute lymphoblastic leukaemia to cutaneous T cell lymphomas. We have compared the toxicities of 2′-deoxyadenosine, 2′-deoxyguanosine, and thymidine for T cell lines derived from patients with T cell acute lymphoblastic leukaemia with those for mature T cell lines derived from patients with cutaneous T cell leukaemia/lymphoma. We have found that both deoxynucleosides are far less toxic to the mature T cell lies than to T lymphoblasts and that the mature cells accumulate much lower amounts of dATP and dGTP when exposed to deoxyadenosine and deoxyguanosine, respectively. Similar studies performed on peripheral blood cells from patients with T cell leukaemias of mature phenotype and on peripheral blood T cells demonstrate similar low amounts of deoxynucleotide accumulation. Measurements of the activities of several purine metabolizing enzymes that participate in deoxynucleoside phosphorylation or degradation do not reveal differences which would explain the toxicity of deoxynucleosides for immature, as compared to mature, T cells. We conclude that deoxynucleoside metabolism in leukaemic T cells varies with their degree of differentiation. These observations may be relevant to the design of chemotherapeutic regimes for T cell malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72479/1/j.1365-2141.1985.tb04067.x.pd

A case of small-cell gastric carcinoma with an adenocarcinoma component and hepatic metastases: treatment with systemic and intra-hepatic chemotherapy.

Primary small-cell carcinoma (SmCC) of the stomach is a rare neoplasm with a poor prognosis and unclear histogenesis: to date, only 50 cases, including ours, have been reported in the literature. In the World Health Organization gastrointestinal tumours’ classification, SmCC of the stomach has been recognized as an ‘independent entity affecting the stomach’. In this paper, the authors present a clinical case and the surgical treatment of an adult with a SmCC of the stomach associated with gastric adenocarcinoma. After laparotomy, a large neoplasm with locoregional extension and multiple liver metastases were found. A palliative resection, subtotal gastrectomy, was performed, followed by systemic and intra-hepatic chemotherapy: computed tomography scan demonstrated a marked response, but the patient died 15 months after the operation. A review of the literature showed that the diagnosis of gastric SmCC is based on immunohistochemical findings. Our experience confirmed the high aggressiveness of this neoplasm, which is generally diagnosed in advanced stage and is unresponsive to chemotherapy, but the combined use of systemic and intra-hepatic chemotherapy shows an acceptable result in a palliative care perspective

Monoclonal antibodies that distinguish non-small cell from small cell lung cancer

Two murine IgG2Ak monoclonal antibodies (703D4, 704A1) were produced and characterized after immunization with a human large cell lung cancer line (NCI-H157). These antibodies detect different epitopes on 31 kilodalton [35S]methionine incorporating protein(s). Radiobinding and immunohistochemical studies show these antibodies bind to most (11/13) human non-small cell lung cancer (adenocarcinoma, epidermoid, and large cell), but not to small cell lung cancer (0/11) tumors tested. The epitopes these antibodies recognized are also expressed on human melanomas (7/8), two other tumors (osteogenic sarcoma, renal cell carcinoma), but not on many other human tumors (breast, colon, neuroblastoma, lymphoid), and not on a panel of normal adult human tissues. Because the antigen(s) are preserved after fixation and because of their ability to distinguish lung cancer types from each other and normal tissues, they should be of clinical, as well as of biologic interest