Granular cell tumor is an uncommon benign tumor occurring on the skin as a single nodule. Multiple tumors are very rare, particularly in children. We describe a child with multiple granular cell tumors on the skin in association with growth hormone deficiency. The occurrence of multiple granular cell tumors in association with other clinical manifestations in childhood is discussed.

Child↗

PubMedDate not supplied

Antitumoral action of 2-deoxy-D-glucose tetraacetate in human melanoma cells.

The ester 2-deoxy-D-glucose tetraacetate (2-DOGTA) was recently shown to display cytostatic and cytotoxic activity in various lines of tumoral cells. In the present work, it was found to inhibit cell growth and confer chemosensitivity to cisplatin in two lines of human melanoma cells, poorly responsive to cisplatin. The inhibition of cell growth by 2-DOGTA was apparently not attributable to alteration of either D-glucose utilization or oxidation in these melanoma cell lines. In freshly isolated human melanoma cells, 2-DOGTA also inhibited cell growth, even in cells resistant to standard chemotherapeutic agents, such as temozolomide, cisplatin and/or vindesine. It is proposed, therefore, that 2-DOGTA should be further investigated for the treatment of melanoma patients, whether alone or in combination with known chemotherapeutic agents.

Adult↗

PubMedDate not supplied

Detection of tumor-associated circulating mRNA in serum, plasma and blood cells from patients with disseminated malignant melanoma.

Reverse transcription polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is a frequently used method for the identification of circulating tumor cells in melanoma patients. The significance and practical value of this procedure for the diagnosis of tumor dissemination in melanoma patients are unclear. The conflicting results may at least partially be related to very low amounts of circulating tumor cells and to our observation that melanoma cells only transiently persist in the peripheral blood. The purpose of the present study was to evaluate the relevance of detection of extracellular melanoma-specific mRNA in serum and plasma samples in comparison to blood cell samples from patients with disseminated disease (stage IV). We therefore compared the presence of specific mRNA for tyrosinase, gp100, and MART-1 by RT-PCR amplification of specific cDNA from serum, plasma, and whole blood samples of 10 melanoma patients. Melanoma-specific mRNA was detectable in whole blood samples of all ten patients tested indicating the presence of circulating melanoma cells. In addition, tyrosinase mRNA could be detected in the serum and/or plasma of 6 of 10 melanoma patients whereas gp100 and MART-1 specific transcripts were not detectable in any of the samples tested. The presence and integrity of amplifiable RNA was shown in all serum and plasma samples of patients and controls by RT-PCR-specific amplification of porphobilinogen deaminase (PBDG) mRNA. We conclude that tyrosinase mRNA but not gp100 and MART-1 mRNA can be amplified from serum and/or plasma in a subset of melanoma patients showing circulating melanoma cells. Therefore, extracellular-directed assays appear to be less sensitive and efficacious in detecting melanoma-specific transcripts compared to cellular-based assays.

Adult↗

PubMedDate not supplied

Immunohistochemical analysis of DNA mismatch-repair enzyme hMSH-2 and Ki-67 in breast carcinomas.

BACKGROUND: The human Mut-S-Homologon-2 (hMSH-2) gene product is a member of a highly conserved family of proteins involved in postrepiclation mismatch repair. MATERIALS AND METHODS: We have analyzed hMSH-2 expression in normal breast tissue (n = 10) and breast carcinomas (n = 30). hMSH-2 protein was investigated immunohistochemically on frozen sections using a specific mouse monoclonal antibody (clone FE11). hMSH-2 labelling pattern was compared with the staining pattern of the proliferation marker Ki-67. A hMSH-2-immunoreactivity score (hMSH-2-IRS) for the semiquantitative analysis of hMSH-2 expression is presented. RESULTS: In normal breast tissue, we only found weak nuclear immunoreactivity for hMSH-2 in 70%, while the remaining 30% were hMSH-2 negative (mean hMSH-2- IRS: 1.00; SD: +/- 0.82). All breast carcinomas analyzed revealed moderate to strong nuclear immunoreactivity (mean hMSH-2-IRS: 7.67; SD: +/- 3.55). hMSH-2 staining was heterogeneous, with visual differences between individual tumour cells. Expression of hMSH-2 protein was consistently and strongly upregulated in tumour cells of breast carcinomas as compared to normal breast tissue. No visual correlation in comparing the labelling patterns for hMSH-2 with the labeliing patterns for Ki-67 (mean percentage of Ki-67 positive tumour cells: 24.33%; SD: +/- 15.35) was observed in breast carcinomas. CONCLUSION: Our findings indicate that (a) hMSH-2 is expressed in normal human breast tissue; (b) expression of hMSH-2 may be of importance for the genetic stability of breast carcinomas in vivo.

Base Pair Mismatch↗

PubMedDate not supplied

Influence of serum prolactin on semen characteristics and sperm function.

The role of serum prolactin (sPRL) in male infertility is still unclear. For assessing the clinical significance of prolactin determination during infertility investigation, serum samples of 204 males attending the Infertility Clinic of Heidelberg were examined during a 1-year period. None of the patients exhibited galactorrhoea or complained of impotence. Results were correlated with age, duration of infertility, sperm count, motility, morphology, viability, and other parameters of routine sperm analysis and postcoital testing (PCT). Additionally, in vitro sperm penetration testing (SCMPT) in cervical mucus of partners and donors was performed as an important measure of functional sperm capacity. The subsequent pregnancy rate was determined after 6 months. Prolactin levels ranged from 1.4 to 24.7 ng/mL, with a median of 5 ng/mL. Only one patient had prolactin levels out of the normal range (greater than 20 ng/mL). No significant correlation of sPRL concentration was found with results of semen analysis, PCT outcome, or SCMPT. The functional sperm capacity was better in the groups of patients with sPRL above the median level (P less than .005). No significant difference in pregnancy rate was found between the high (greater than 5 ng/mL) and low (less than or equal to 5 ng/mL) prolactin groups; these were 20% and 26%, respectively. The results suggest that routine screening of asymptomatic male patients during infertility investigation for sPRL concentration is not helpful for assessing fertility prognosis. Prolactin should be preferentially determined in patients with clinical symptoms of hyperprolactinemia to exclude pituitary adenoma.

Adult↗

PubMedDate not supplied

Clusterin (CLU) and melanoma growth: CLU is expressed in malignant melanoma and 1,25-dihydroxyvitamin D3 modulates expression of CLU in melanoma cell lines in vitro.

BACKGROUND: The glycoprotein clusterin (CLU) has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. CLU expression has been associated with tumorigenesis and the progression of various malignancies. MATERIALS AND METHODS: The expression of CLU was studied immunohistochemically in paraffin sections of primary cutaneous malignant melanomas, metastases of malignant melanomas and acquired melanocytic naevi. Using PCR and Western blotting, the expression of CLU was also investigated in various vitamin D-responsive (MeWo, SK-MEL-28) and vitamin D-resistant melanoma cell lines (SK-MEL-5, SK-MEL-25), as well as in normal human melanocytes (NHM), along with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] treatment. RESULTS: In contrast to acquired melanocytic naevi, CLU immunoreactivity was found in primary cutaneous malignant melanomas and metastases of malignant melanomas in situ. Both CLU protein and RNA were detected in melanoma cell lines and NHM. Treatment with 1,25(OH)2D3 modulated CLU's expression in vitamin D-responsive but not in -resistant melanoma cell lines. CONCLUSION: CLU may be of importance for the progression of malignant melanoma. The growth regulatory effects of 1,25(OH)2D3 in melanoma cell lines may, at least in part, be mediated via modulation of CLU expression.

Adult↗