Dynamic instability of microtubules is critical for mitotic spindle assembly and disassembly during cell division, especially in rapidly dividing tumor cells. Microtubule-associated proteins (MAPs) are a family of proteins that influence this property. We showed previously that MAP2, a neuron-specific protein that stabilizes microtubules in the dendrites of postmitotic neurons, is induced in primary cutaneous melanoma but is absent in metastatic melanomas. We proposed that induction of a microtubule-stabilizing protein in primary melanoma could disrupt the dynamic instability of microtubules, inhibit cell division and prevent or delay tumor progression. Although a number of clinical and pathological factors that influence melanoma progression have been identified, to date there is no single histological, immunohistochemical, serological, or molecular marker that accurately predicts aggressive behavior of melanoma. 1 Tumor thickness, which is considered the best predictor of melanoma aggressiveness, is not always a reliable parameter and is not relevant for more advanced primary tumors and metastatic disease.1,2 Therefore, there is a need for identification of molecular markers that predict biological behavior of melanoma cells independent of tumor thickness.Melanoma exhibits plasticity of differentiation and is known to differentiate along multiple, including endothelial and neuronal, cellular pathways.3 However, the effects of transdifferentiation of melanoma cells on tumor progression are not well understood. Earlier, we showed that MAP2 (microtubule-associated protein 2), a neuronspecific protein, is expressed abundantly in early invasive primary melanoma lesions (by immunohistochemistry) and primary melanoma cell lines (by Northern and western blot analyses) but is absent in metastatic melanomas lesions and cell lines. 4 In addition to primary melanomas 5 expression of MAP2 has been reported in other cutaneous tumors with neuroendocrine differentia-

Melastatin 1 (MLSN1), originally identified as melanoma metastasis suppressor, represents a TRPM subfamily of transient receptor potential (TRP) proteins which serve diverse biological roles in a wide variety of cell types. Down-regulation of MLSN1 expression in human cutaneous melanoma, as indicated by in situ hybridization, appears to be a prognostic marker for melanoma metastasis. However, the exact physiological function(s) of MLSN1, the mechanism(s) involved in the regulation of its expression and its role in melanoma tumour progression are not yet clear. In this study, we identified a 654 bp upstream sequence of MLSN1, containing four E boxes (E1-E4), including an 11 bp M box (E4), that is sufficient for melanocyte-specific transcription and activation by the melanocyte transcription factor MITF (a bHLH-zip factor). Deletion analysis showed that the two distal E boxes (E3 and E4) in the MLSN1 promoter are required for both its activation by MITF and its constitutive activity in melanoma cells. Western blot analysis using polyclonal rabbit anti-human MLSN1 antibodies identified several polypeptides, presumably generated by both alternative splicing of MLSN1 messenger RNA (mRNA) and proteolytic cleavage, in both melanocytes and metastatic melanoma cells. Thus, multiple mechanisms appear to regulate MLSN1 expression in melanocytes and melanoma cells.

No abstract

No abstract

Objective  To evaluate the role of the Gleason score of needle biopsies of the prostate in predicting the final pathological staging of patients with carcinoma of the prostate treated by radical prostatectomy. Patients and methods  The records of 466 patients with carcinoma of the prostate treated by radical prostatectomy were reviewed, comparing the Gleason scores of the core‐needle biopsies with the Gleason score and final pathological staging of the surgical specimens. Results  The biopsy grade was the same as that of the prostatectomy specimen in 54% of the patients. The most common discordance was the upgrading of well‐differentiated tumours in 75% of the patients. When the biopsy grade was compared with the surgical pathological stage, 49% of low‐ and 82% of high‐grade lesions in the biopsy had capsular penetration by tumour or locally advanced disease (Stage C and D1). Conclusion  Well‐differentiated tumours on the biopsy core are not predictive of organ‐confined disease, but a poorly differentiated lesion is a good indicator of extracapsular extension of the cancer.

Delayed hemorrhage is an uncommon complication following PCNL that can be successfully managed with conservative management; only a few patients will require angiography and then embolization. Tubeless PCNL significantly predicted the occurrence of severe postoperative bleeding.

It seems that using spinal anesthesia by intrathecal injection of local anesthetic solutions vs general anesthesia has comparable surgical outcomes and reduces the requirement for analgesia after PCNL in the early postoperative period.

The proposed surgical modifications are based on 14 years of experience and 1510 cases, and make LDN simple, safe, and cost-effective. The excellent recipient and graft outcomes with minimal morbidity obtained further confirm that LDN can be considered as the gold standard for kidney donation surgery.