Phosphatases in the cell surface of living yeast cells /

Work performed at the University of Rochester.

Further studies of bone isografts in diffusion chambers; final progress report.

Mode of access: Internet.

A peculiar and unusual disease of the osseous tissue in the horse : resembling, in many of its characteristics, Mollities ossium, Rhachitis, Osteoporosis, and fatty degeneration of bone /

"Reprinted from the 'Veterinarian'."

Hereditary fragility of bone (fragilitas osseus, osteopsathyrosis)

Mode of access: Internet.

Merkel-cell carcinoma of the skin

Merkel-cell carcinoma (MCC) is a rare form of skin cancer of neuroendocrine origin that has been described as the most aggressive cutaneous malignancy. The cell of origin is thought to be the Merkel cell or skin-pressure receptor. It has the propensity for dermal-lymphatic invasion, and nodal and haematogenous spread. Factors that have been implicated in its cause include exposure to sunlight and immunosuppression. The tumour has many similarities to small-cell carcinoma of the lung, with intrinsic sensitivity to ionising radiation and chemotherapy, and an aggressive metastatic potential. The best treatment outcomes can be achieved with early diagnosis and the integration of surgery, radiation, and chemotherapy. The treatment challenges for the clinician are often enormous because many of the patients are elderly and because lesions occur in difficult sites such as the head and neck region and the lower leg.

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.

Role of dietary factors in the development of basal cell cancer and squamous cell cancer of the skin

The role of dietary factors in the development of skin cancer has been investigated for many years; however, the results of epidemiologic studies have not been systematically reviewed. This article reviews human studies of basal cell cancer (BCC) and squamous cell cancer (SCC) and includes all studies identified in the published scientific literature investigating dietary exposure to fats, retinol, carotenoids, vitamin E, vitamin Q and selenium. A total of 26 studies were critically reviewed according to study design and quality of the epidemiologic evidence. Overall, the evidence suggests a positive relationship between fat intake and BCC and SCC, an inconsistent association for retinol, and little relation between beta-carotene and BCC or SCC development. There is insufficient evidence on which to make a judgment about an association of other carotenoids with skin cancer. The evidence for associations between vitamin E, vitamin C, and selenium and both BCC and SCC is weak. Many of the existing studies contain limitations, however, and further well-designed and implemented studies are required to clarify the role of diet in skin cancer. Additionally, the role of other dietary factors, such as flavonoids and other polyphenols, which have been implicated in skin cancer development in animal models, needs to be investigated.

NF-gamma B - a target in the inflammation of bone destruction

NF-kappaB activation is associatied with the inflammation of bone destruction and certain cancers. The NEMO (NF-kB essential modulator)-binding domain (NBD) protein inhibits the activation of NF-kappaB. Cellular studies have shown that the NBD protein inhibits osteoclastogenesis. Mimicking infection with a lipopolysaccharide injection in mice resulted in activated osteoclasts and reduced bone mineral density. These responses are inhibited with the NBD peptide. In a mouse model of rheumatoid arthritis, collagen-induced arthritis, treatment with the NBD protein delayed the onset, lowered the incidence and decreased the severity of the arthritis. NF-kappaB is a target in the inflammation associated with bone destruction. A key issue is whether or not this important transcription factor can be inhibited without causing excessive adverse effects and/or toxicity.

Total pharyngolaryngectomy for squamous cell carcinoma of the hypopharynx: A review

Objectives. To evaluate our experience with total pharyngolaryngectomy in the treatment of hypopharyngeal squamous cell carcinoma. Study Design: Retrospective analysis of consecutively treated patients in an academic otolaryngology, head and neck department. Methods. One hundred eighty patients who had total pharyngolaryngectomy performed for hypopharyngeal carcinoma were included in this study. Patients with a history of previous head and neck cancer were excluded. Clinicopathologic parameters were recorded and survival calculated using the Kaplan-Meier method. Results. One hundred sixty-two (90%) of the patients were male, and the patients had a mean age of 62 years. The majority (91%) of patients had advanced overall clinical stage disease (stage 3,4). Thirty-one (17.8%) and 43 (24%) patients developed locoregional and metastatic disease recurrence, respectively. The 2- and 5-year disease-specific survival rates were 72% and 52%, respectively. Advanced nodal stage, perineural invasion, lymphovascular invasion, and positive margins were predictors of poor survival on univariate analysis, and lymphovascular invasion was an independent prognostic factor on multivariate analysis. Conclusion: Surgery and postoperative radiotherapy remains the treatment against which other modalities should be compared for advanced stage hypopharyngeal squamous cell carcinoma.

Live cell imaging of heavy-ion-induced radiation responses by beamline microscopy

To study the dynamics of protein recruitment to DNA lesions, ion beams can be used to generate extremely localized DNA damage within restricted regions of the nuclei. This inhomogeneous spatial distribution of lesions can be visualized indirectly and rapidly in the form of radiation-induced foci using immunocytochemical detection or GFP-tagged DNA repair proteins. To analyze faster protein translocations and a possible contribution of radiation-induced chromatin movement in DNA damage recognition in live cells, we developed a remote-controlled system to obtain high-resolution fluorescence images of living cells during ion irradiation with a frame rate of the order of seconds. Using scratch replication labeling, only minor chromatin movement at sites of ion traversal was observed within the first few minutes of impact. Furthermore, time-lapse images of the GFP-coupled DNA repair protein aprataxin revealed accumulations within seconds at sites of ion hits, indicating a very fast recruitment to damaged sites. Repositioning of the irradiated cells after fixation allowed the comparison of live cell observation with immunocytochemical staining and retrospective etching of ion tracks. These results demonstrate that heavy-ion radiation-induced changes in sub-nuclear structures can be used to determine the kinetics of early protein recruitment in living cells and that the changes are not dependent on large-scale chromatin movement at short times postirradiation. © 2005 by Radiation Research Society.