Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, PTEN, that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions.

https://science.sciencemag.org/content/sci/275/5308/1943.full.pdf

PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

http://orion.bme.columbia.edu/lulab/pdf/Altman_Silk-Based-Biomaterials_2003.pdf

Silk-based biomaterials

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation. An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. This paper describes the first extensive map of human DNaseI hypersensitive sites — markers of regulatory DNA — in 125 diverse cell and tissue types. Integration of this information with other data sets generated by ENCODE (Encyclopedia of DNA Elements) identified new relationships between chromatin accessibility, transcription, DNA methylation and regulatory-factor occupancy patterns. Evolutionary-conservation analysis revealed signatures of recent functional constraint within DNaseI hypersensitive sites.

/pdf/the-accessible-chromatin-landscape-of-the-human-genome-2cq94d4b48.pdf

The accessible chromatin landscape of the human genome

Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN

The athymic (nude) mouse is a useful model for studying the biology and response to therapies of human tumors in vivo. A survey of recent literature revealed the use of 19 different formulas for determining the size of subcutaneous tumors grown as xenografts in nude mice (2 for determining tumor area, 3 for tumor diameter, and 14 for calculating tumor volume). We compared the volumes, areas, and diameters predicted by each of the 19 formulas with the actual weights of 50 tumors ranging from 0.46 to 22.0 g established in nude mice as xenografts from human cell lines. In addition to determining how well each formula predicted relative tumor size, we analyzed how well each formula estimated actual tumor mass. The ellipsoid volume formulas (π/6 x L x W x H and 1/2 x L x W x H) were best for estimating tumor mass (r=0.93), whereas measurements of diameter correlated poorly with tumor mass (r<0.66). Although determination of tumor area correlated well with tumor mass in small tumors (r=0.89), correlations of area with tumor mass for large tumors were poor (r=0.41). We conclude that determination of the ellipsoid volume from measurements of three axes consistently yields the most accurate estimations of both relative and actual tumor mass.

Determination of subcutaneous tumor size in athymic (nude) mice

We have utilized intraoperative stimulation to establish the functional nature of tissue to be biopsied in 20 patients undergoing CT-guided stereotactic biopsies. We have performed from 1–4 stimulatio

Use of Intraoperative Stimulation in the Selection of Target Sites for CT-Guided Stereotactic Biopsies

Study Design This is a retrospective review of a prospectively maintained database of anterior cervical discectomy and fusion with plating (ACDFP) cases. Objective The aim of this study is to evaluate within a clinical practice evidence-based results of short-term morbidity with multilevel ACDFP. Methods Clinical morbidity, length of hospital stay, visual analog scale (VAS) and Odom scores, Neck Disability Index (NDI), hardware failure, and return-to-work (RTW) status were prospectively collected in an electronic database for 678 patients who underwent 1-, 2-, 3-, or 4-level ACDFP during an 8-year period. A total of 519 patients met the study criteria and were retrospectively analyzed. Results The majority of all patients noted "Excellent" or "Good" status for 1 month (91%), 2 months (92%), and 3 months (96%). Patients with 1-, 2-, and 3-level ACDFP returned to work sooner, 60% at 1 month, 70% at 2 months, and 68% at 3 months. For 4-level patients, the majority did not RTW until 3 months (71%). The only significant increase in morbidity with increasing levels was hospital stay for 3- and 4-level ACDFP and RTW for 4-level ACDFP. Conclusion Multilevel ACDFP can be performed with low initial morbidity. An individual practice can review results to allow for ongoing evidence-based care. [Table: see text].

/pdf/early-morbidity-of-multilevel-anterior-cervical-discectomy-25xe0ydgjr.pdf

Early Morbidity of Multilevel Anterior Cervical Discectomy and Fusion with Plating for Spondylosis: Does the Number of Levels Influence Early Complications? A Single Surgeon's Experience in 519 Consecutive Patients.

IN VITRO RESPONSE OF CELLS DERIVED FROM HUMAN GLIOMAS (HGL) TO DIBUTYRYL ADENOSINE 3′:5′-CYCLIC MONOPHOSPHATE (cAMP)

Central nervous system (CNS) malignancies represent one ofthe most devastating forms of cancer. Malignant gliomas, the most commonly occurring primary tumor of the CNS, have a particularly bleak prognosis despite surgery and combined radiation and chemotherapy (1, 2). Immunological approaches to diagnosis and treatment have seemed attractive, but in the past have been frustrated by technological limitations (3, 4). Monoclonal antibody methodology offers major advantages over conventional methods of antiserum production: a practically unlimited source of homogeneous, highly specific reagent which may be prepared using impure or complex antigens. This has led to a new age in neuroimmunology and neuro-oncology, with the potential for better understanding of the basic cell biology of CNS neoplasia, and for improvement in diagnosis, imaging, and therapy.

Dennis E. Bullard

Papers

Use of Intraoperative Stimulation in the Selection of Target Sites for CT-Guided Stereotactic Biopsies

Early Morbidity of Multilevel Anterior Cervical Discectomy and Fusion with Plating for Spondylosis: Does the Number of Levels Influence Early Complications? A Single Surgeon's Experience in 519 Consecutive Patients.

IN VITRO RESPONSE OF CELLS DERIVED FROM HUMAN GLIOMAS (HGL) TO DIBUTYRYL ADENOSINE 3′:5′-CYCLIC MONOPHOSPHATE (cAMP)

The Applications of Monoclonal Antibodies in Neuro-Oncology