Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments

Recent studies have shown that the transport of microtubules (MTs) and neurofilaments (NFs) within the axon is rapid, infrequent, asynchronous, and bidirectional. Here, we used RNA interference to investigate the role of cytoplasmic dynein in powering these transport events. To reveal transport of MTs and NFs, we expressed EGFP-tagged tubulin or NF proteins in cultured rat sympathetic neurons and performed live-cell imaging of the fluorescent cytoskeletal elements in photobleached regions of the axon. The occurrence of anterograde MT and retrograde NF movements was significantly diminished in neurons that had been depleted of dynein heavy chain, whereas the occurrence of retrograde MT and anterograde NF movements was unaffected. These results support a cargo model for NF transport and a sliding filament model for MT transport

Metastatic Melanoma to the Bladder: Case Report and Review of the Literature.

A 49-year-old Caucasian woman presented to the dermatology clinic for follow-up of malignant melanoma with a complaint of painless gross hematuria. Two years prior she was diagnosed with malignant melanoma from a skin lesion on her left flank treated with wide excision, negative axillary sentinel lymph node biopsy, and adjuvant radiotherapy. Subsequently, she had no evidence of disease until urologic evaluation of her hematuria revealed two lesions in her bladder and cytopathology demonstrated findings consistent with malignant melanoma. We review literature on melanoma metastatic to the bladder and discuss the potential role of metastasectomy and other treatment strategies in such rare cases

Low-grade serous carcinoma (mullerian/ovarian type) of the paratestis presenting as diffuse metastatic disease of unknown origin: Case report of an uncommon tumor with an unusual presentation

Low-grade (papillary) serous carcinoma of ovarian type is rare in males and histologically identical to low-grade serous carcinomas in female patients. We present a case of paratesticular low-grade serous carcinoma in a 42year old male, with the highly unusual initial presentation as diffuse metastatic disease in the abdomen. Imaging revealed a cystic lesion of the right testis/hemiscrotum. Biopsy of the abdominal metastasis and subsequent right orchiectomy specimen showed invasive papillary serous carcinoma, low grade, with prominent psammomatous calcifications. Immunohistochemically, both tumors were positive for PAX8, WT-1, CA-125 and cytokeratin CK7, and negative for mesothelioma markers (calretinin, D2-40) and CD10. The main differential diagnoses for this tumor include mesothelioma of tunica vaginalis, adenocarcinoma of rete testis/epididymis and metastases. Although rare as an initial presentation, ovarian type serous carcinoma of the paratestis should be included in the differential diagnosis in males with abdominal metastases that show papillary architecture, psamommatous calcifications and PAX8 immunoreactivity

Incorporating Oxygen-Enhanced MRI into Multi-Parametric Assessment of Human Prostate Cancer

Hypoxia is associated with prostate tumor aggressiveness, local recurrence, and biochemical failure. Magnetic resonance imaging (MRI) offers insight into tumor pathophysiology and recent reports have related transverse relaxation rate (R2*) and longitudinal relaxation rate (R1) measurements to tumor hypoxia. We have investigated the inclusion of oxygen-enhanced MRI for multi-parametric evaluation of tumor malignancy. Multi-parametric MRI sequences at 3 Tesla were evaluated in 10 patients to investigate hypoxia in prostate cancer prior to radical prostatectomy. Blood oxygen level dependent (BOLD), tissue oxygen level dependent (TOLD), dynamic contrast enhanced (DCE), and diffusion weighted imaging MRI were intercorrelated and compared with the Gleason score. The apparent diffusion coefficient (ADC) was significantly lower in tumor than normal prostate. Baseline R2* (BOLD-contrast) was significantly higher in tumor than normal prostate. Upon the oxygen breathing challenge, R2* decreased significantly in the tumor tissue, suggesting improved vascular oxygenation, however changes in R1 were minimal. R2* of contralateral normal prostate decreased in most cases upon oxygen challenge, although the differences were not significant. Moderate correlation was found between ADC and Gleason score. ADC and R2* were correlated and trends were found between Gleason score and R2*, as well as maximum-intensity-projection and area-under-the-curve calculated from DCE. Tumor ADC and R2* have been associated with tumor hypoxia, and thus the correlations are of particular interest. A multi-parametric approach including oxygen-enhanced MRI is feasible and promises further insights into the pathophysiological information of tumor microenvironment

Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma

AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development