Citations

The objective of the current study was to determine the suitability of cell-laden and cell-free alginate–gelatin biopolymer hydrogel for osteochondral restoration in a sheep model ( n = 12). Four femoral defects per animal were filled with hydrogel (cHG) plus autologous chondrocytes (cHG + C) or periosteal cells (cHG + P) or gel only (cHG) or were left untreated (E). In situ solidification enabled instantaneous implant fixation. Sixteen weeks postoperatively, defect sites were processed for light microscopy and immunofluorescence. A modified Mankin and a semi-quantitative immunoreactivity score were used to evaluate histology and immunofluorescence, respectively. Defects after cHG + C were restored with smooth, hyaline-like neo-cartilage and trabecular subchondral bone. cHG + P and cHG treatments revealed slightly inferior regenerate morphology. Undifferentiated tissue was found in E. The histological score showed significant ( p < 0.05) differences between all treatment groups. In conclusion, cHG induces satisfactory defect regeneration. Complete filling of the cavity in one step and subsequent rapid in situ solidification was feasible and facilitated graft fixation. Cell implantation might be beneficial, because cells seem to play a key role in histological outcome. Still, their contribution to the repair process remains unresolved because host cell influx takes place. The combination of alginate and gelatin, however, creates an environment capable of serving implanted and host cells for osteo-chondrogenic tissue regeneration.

Abstract Rationale The 2002 American Thoracic Society/European Respiratory Society classification of idiopathic interstitial pneumonias identified nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis. Concern was expressed that NSIP was a “wastebasket” category, difficult to distinguish from other idiopathic interstitial pneumonias. Objectives The following questions were addressed: (1) Is idiopathic NSIP a distinct entity? 2) If so, what are its clinical, radiologic and pathologic characteristics? (3) What is the role of radiology and pathology in establishing the diagnosis? (4) To make a diagnosis of idiopathic NSIP, what other disorders need to be excluded and how should this be done? Methods Investigators who had previously reported cases of idiopathic NSIP were invited to submit cases for review (n = 305). After initial review, cases with complete clinical, radiologic, and pathologic information (n = 193) were reviewed in a series of workshops. Measurements and Main Results Sixty-seven cases were identified as NSIP. Mean age was 52 years, 67% were women, 69% were never-smokers, and 46% were from Asian countries. The most common symptoms were dyspnea (96%) and cough (87%); 69% had restriction. By high-resolution computed tomography, the lower lung zones were predominantly involved in 92% of cases; 46% had a peripheral distribution; 47% were diffuse. Most showed a reticular pattern (87%) with traction bronchiectasis (82%) and volume loss (77%). Lung biopsies showed uniform thickening of alveolar walls with a spectrum of cellular to fibrosing patterns. Five-year survival was 82.3%. Conclusions Idiopathic NSIP is a distinct clinical entity that occurs mostly in middle-aged women who are never-smokers. The prognosis of NSIP is very good.

Abstract Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02% and 0.2% of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in 40% to 70% of patients at the time of diagnosis. Standard chemotherapy with mitotane is often ineffective with intolerable side effects. The modern molecular technology of comparative genomic hybridization allows the examination of DNA for chromosomal alterations, which can lend biological insight into cancer processes. Genomes of 25 ACC clinical samples were queried on the Agilent 44K Human Genome comparative genomic hybridization array detecting regions of chromosomal gain and loss within the tumor population. Commonly shared amplifications appearing in ≥50% of tumors at P ≤ 10−4 include regions within chromosomes 5, 7, 12, 16q, and 20. Deleted genomic regions within ACC include portions of chromosomes 1, 3p, 10q, 11, 14q, 15q, 17, and 22q. Genomic aberrations in regions associated with differential survival (P ≤ 0.05) and presence in ≥20% of tumors include amplifications of 6q, 7q, 12q, and 19p. Deletions within stratified survival groups include localized regions within 3, 8, 10p, 16q, 17q, and 19q. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation-dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. [Mol Cancer Ther 2008;7(2):425–31]

Abstract Hyperdiploid multiple myeloma (H-MM) is the most common form of myeloma. In this gene expression profiling study, we show that H-MM is defined by a protein biosynthesis signature that is primarily driven by a gene dosage mechanism as a result of trisomic chromosomes. Within H-MM, four independently validated patient clusters overexpressing nonoverlapping sets of genes that form cognate pathways/networks that have potential biological importance in multiple myeloma were identified. One prominent cluster, cluster 1, is characterized by high expression of cancer testis antigen and proliferation-associated genes. Tumors from these patients were more proliferative than tumors in other clusters (median plasma cell labeling index, 3.8; P &lt; 0.05). Another cluster, cluster 3, is characterized by genes involved in tumor necrosis factor/nuclear factor-κB signaling and antiapoptosis. These patients have better response to bortezomib as compared with patients within other clusters (70% versus 29%; P = 0.02). Furthermore, for a group of patients generally thought to have better prognosis, a cluster of patients with short survival (cluster 1; median survival, 27 months) could be identified. This analysis illustrates the heterogeneity within H-MM and the importance of defining specific cytogenetic prognostic factors. Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients. [Cancer Res 2007;67(7):2982–9]

Abstract A policy of supportive treatment is frequently adopted for patients with metastatic disease to the adrenal glands. This study reports an experience with adrenalectomy for adrenal metastasis. Between 1983 and 1993, adrenalectomy was performed in 52 patients for metastasis to the adrenal glands. Survival was calculated by the Kaplan- Meier method and compared with the log rank test. Primary tumour sites included kidney (n = 15), lung (n = 11), colon (n = 7), unknown (n = 5), stomach (n = 3), melanoma (n = 3) and other (n = 8). Adenocarcinoma (69 per cent) was the most common histological cell type. Thirty-two patients were asymptomatic on initial evaluation. Symptomatic adrenal pain relief was achieved in 11 of 13 patients. Overall survival rates were 73 per cent at 1 year and 40 per cent at 2 years. Patients with potentially curative resection had better survival than those who had a palliative procedure. Patients with adrenal metastases due to adenocarcinoma had improved survival compared with that in those with other histological cell types. Although long-term survival is generally poor, highly selected patients with adrenal metastasis (symptomatic disease or adenocarcinoma) may benefit from surgical resection.

The practice of oncology can be a source of both great satisfaction and great stress. Although many oncologists experience burnout, depression, and dissatisfaction with work, others experience tremendous career satisfaction and achieve a high overall quality of life. Identifying professional goals, optimizing career fit, identifying and managing stressors specific to practice type, and achieving the optimal personal work–life balance can increase the likelihood of individual oncologists' achieving personal and professional satisfaction. In this article, we will explore how oncologists can accomplish these tasks and will examine several pervasive professional myths that often distort perspective. The article concludes in a conversation with four oncologists regarding what they find most meaningful about their work, how they manage career-specific stressors, and how they achieve balance between their personal and professional lives.

The tau (MAPT) locus exists as two distinct clades, H1 and H2. The H1 clade has a normal linkage disequilibrium structure and is the only haplotype found in all populations except those derived from Caucasians. The H2 haplotype is the minor haplotype in Caucasian populations and is not found in other populations. It shows no recombination over a region of 2 Mb with the more common H1 haplotype. The distribution of the haplotype and analysis of the slippage of dinucleotide repeat markers within the haplotype suggest that it entered Homo sapiens populations between approx. 10000 and 30000 years ago. However, sequence comparison of the H2 haplotype with the H1 haplotype and with the chimp sequence suggests that the common founder of the H1 and H2 haplotypes was far earlier than this. We suggest that the H2 haplotype is derived from Homo neanderthalensis and entered H. sapiens populations during the co-existence of these species in Europe from approx. 45000 to 18000 years ago and that the H2 haplotype has been under selection pressure since that time, possibly because of the role of this H1 haplotype in neurodegenerative disease.