Small cell lung cancer can express CD34 antigen.

In humans CD34 is a valid and reliable marker for hematopoletic stem and progenitor cells. In general, solid tumors, with the exception of endothelial cancers, do not express CD34. Accordingly, immunological selection of CD34+ hematopoietic stem/progenitor cells can be used to remove CD34- malignant cells in the setting of autotransplantation. To rule out CD34 expression on tumor cells from small cell lung cancer (SCLC), eleven SCLC cell lines were analyzed by flow cytometry. Interestingly, two of these were positive for CD34 and their expression of full-length CD34 was further confirmed by reverse transcriptase and polymerase chain reaction (RT-PCR). This finding indicates that prior to subjecting SCLC patients to the above treatment modality, preparing CD34+ hematopoietic stem/progenitor cells from SCLC patients for autotransplantation, CD34 expression on their tumor cells should be screened using immunohistochemistry and/or flow cytometry.

Double high-dose chemotherapy supported by autologous transplantation of peripheral blood stem cells for treatment of an elderly patient with small-cell lung cancer.

We report a 62-year-old male with extensive disease small-cell lung cancer (SCLC) who was successfully treated with double high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT). This patient achieved a partial response with 3 cycles of induction chemotherapy. After the peripheral blood stem cell mobilization, two cycles of high-dose ICE regimen (ifosfamide 3,000 mg/m2 at days 1 to 5, carboplatin 400 mg/m2 at days 1, 3, 5, and etoposide 500 mg/m2 at days 1, 3, 5) could be given with further regression of the tumor and acceptable toxicities. This successful case suggests the feasibility of double high-dose ICE with auto-PBSCT in elderly patients with SCLC.

SHP-1/immunoreceptor tyrosine-based inhibition motif-independent inhibitory signalling through murine natural killer cell receptor Ly-49A in a transfected B-cell line.

Ly-49A is a member of the Ly-49 family of mouse natural killer cell receptors that inhibit cytotoxicity upon recognition of their ligands, the major histocompatibility complex (MHC) class I molecules, on the target cell surface. Although Ly-49A has an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail, relatively little is known about the mechanisms underlying its inhibitory function. We report here that antibody-mediated co-ligation of the B-cell receptor (BCR) with the transfected Ly-49A molecule results in abrogation of BCR-induced interleukin-2 (IL-2) secretion and mild reduction in activation of Erk1/2 and p38 mitogen-activated protein (MAP) kinases in the B-cell line A20. Surprisingly, BCR-induced calcium mobilization was unaffected by cross-linking of BCR with Ly-49A. Furthermore, substitution of the single tyrosine residue in ITIM with phenylalanine, did not result in a complete loss of inhibitory function, as measured by BCR-induced IL-2 secretion. Deletion of the N-terminal 37 amino acid peptide, which includes the ITIM, did abrogate the inhibitory activity. Co-immunoprecipitation experiments revealed that, upon induction of tyrosine phosphorylation, Ly-49A recruits tyrosine phosphatase src-homology 2 (SH2) containing tyrosine phosphatases-1 (SHP-1), but not inositol phosphatase src-homology 2 (SH2) containing inositol phosphatase (SHIP), and that the tyrosine residue in the ITIM is critical for this interaction. These results suggest that transfected Ly-49A utilizes two different inhibitory mechanisms in B-cell signalling: ITIM-dependent and ITIM-independent.