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Biomedical subjects

M Kauffman

Publications and source records attributed to M Kauffman.

8 recordsLinked to original sources

A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma.

In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.

Adult↗

Melastatin expression and prognosis in cutaneous malignant melanoma.

PURPOSE: Melastatin (MLSN-1), a novel melanocyte-specific gene recently identified using a genomic approach, is expressed in murine and human melanoma cells at levels inversely proportional to metastatic rates in vivo. We studied the relationship between expression of melastatin mRNA in the primary cutaneous tumor and prognosis in patients with localized malignant melanoma. PATIENTS AND METHODS: Melastatin mRNA was evaluated by in situ hybridization in primary cutaneous melanoma from 150 patients with localized disease (American Joint Committee on Cancer [AJCC] stage I and II). Multivariate Cox proportional hazards regression analysis was performed to assess the prognostic utility of melastatin mRNA expression while adjusting for other prognostic indicators. RESULTS: Uniform melastatin mRNA expression in the primary tumor was correlated with prolonged disease-free survival (P < .0001). Multivariate analysis revealed that melastatin status, mitotic rate, and tumor thickness influence disease-free survival independently. The 8-year disease-free survival rate in AJCC stage I patients whose tumors diffusely expressed melastatin mRNA was 100%, whereas in stage I patients with melastatin loss, the disease-free survival rate was 77% +/- 15% (median +/- SE). In patients with stage II disease whose tumors diffusely expressed melastatin mRNA, the 8-year disease-free survival rate was 90% +/- 7%, whereas in patients with melastatin loss, the disease-free survival rate was 51% +/- 8%. CONCLUSION: Downregulation of melastatin mRNA in the primary cutaneous tumor is a prognostic marker for metastasis in patients with localized malignant melanoma and is independent of tumor thickness and other variables. Used in combination, melastatin status and tumor thickness allow for the identification of subgroups of patients at high and low risk of developing metastatic disease.

Adult↗

A TM3-like MADS-box gene from Eucalyptus expressed in both vegetative and reproductive tissues.

MADS-box genes in plants are a diverse class of transcription factors that are involved in regulating developmental processes, particularly meristem and organ identity during floral development. They are characterized by a highly conserved MADS-box domain of 59 amino acids that binds to specific DNA sequences. We report the characterization of a cDNA clone, ETL (Eucalyptus TM3 Like), from Eucalyptus globulus subspecies bicostata encoding a putative transcription factor of the MADS-box class that is strongly expressed in both vegetative and floral tissues, suggesting that it regulates processes other than floral development. The clone was isolated from a floral bud cDNA library with a probe generated from Eucalyptus genomic DNA by PCR using degenerate primers to the MADS-box of the floral regulatory gene APETALA 1. The ETL cDNA clone encodes a putative protein of 206 amino acids that contains an N-terminal MADS-box and a helical domain of approx. 60 amino acids predicted to form a coiled-coil (K-box). These structural features are characteristic of plant MADS-box proteins. The MADS-box domain contains all the signature residues of a class of MADS-box genes typified by the tomato gene TM3 and overall, ETL shows 56% amino acid identity to TM3. Like TM3, the ETL gene is expressed in both vegetative and reproductive organs, predominantly in root and shoot meristems and organ primordia, as well as in developing male and female floral organs.

Amino Acid Sequence↗