Change in proteoglycan metabolism is a characteristic of human patellar tendinopathy

Objective

To determine differences in the metabolism of proteoglycans and the gene expression of proteinases and their inhibitors between patellar tendons exhibiting chronic overuse tendinopathy and normal patellar tendons in humans.

Methods

Rates of loss and synthesis of proteoglycans were determined. Radiolabeled and total proteoglycans retained in and lost from the tissue were analyzed by fluorography and Western blotting. Levels of messenger RNA for matrix metalloproteinase 1 (MMP‐1), MMP‐2, MMP‐3, MMP‐9, MMP‐13, ADAMTS‐1, ADAMTS‐4, ADAMTS‐5, tissue inhibitor of metalloproteinases 1 (TIMP‐1), TIMP‐2, TIMP‐3, and TIMP‐4 were determined in fresh tissue.

Results

The rate of loss of ³⁵S‐labeled proteoglycans was greater in abnormal tendons, as was the rate of synthesis of proteoglycans. Fluorography and Western blotting revealed the presence of greater amounts of large proteoglycans (aggrecan and versican) in abnormal tendons, and these proteoglycans were rapidly lost from the matrix of abnormal tendons. There was no significant difference in the expression of ADAMTS‐1, ADAMTS‐4, ADAMTS‐5, MMP‐1, MMP‐2, MMP‐3, MMP‐13, TIMP‐2, TIMP‐3, or TIMP‐4. There was a significant increase in the expression of MMP‐9 and TIMP‐1 in abnormal tendons.

Conclusion

Our findings suggest that a change in the proteoglycan content of the extracellular matrix in abnormal tendons results from the altered metabolism of the cells, reflected in the enhanced synthesis of the large proteoglycans aggrecan and versican, and does not appear to result from changes at the level of gene expression.

     

Angiogenesis: a prognostic determinant in pancreatic cancer?

Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.     

The impact of genomics on the management of myeloma

Myeloma is a complex disease, characterized by a wide heterogeneity in clinical presentation, evolution, and molecular portraits. The successive use of cytogenetics, molecular cytogenetics, expression genomics, copy number genomics, and, more recently, deep sequencing, has shown that this heterogeneity can be used to identify markers usable for not only prognostication but also therapeutic choice and, ultimately, discovery of druggable targets. The use of some of these techniques is now mandatory for the management of patients. Although risk-adapted therapy is not yet a routine practice in myeloma, these molecular changes are essential for the definition of the prognosis.     

The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer

NAD(P)H:quinone oxidoreductase 1 (NQO1), is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones into hydroquinones. A polymorphism (NQO1*2) alters enzymatic activity of NQO1 resulting in diminished NQO1 activity. Malignancies with NQO1*2 may be resistant to radiation and chemotherapy with resulting poorer survival. NQO1 allele was evaluated in subjects enrolled in ECOG 3590, a randomized comparison of radiation (RT) vs radiation and chemotherapy with cisplatin/etoposide (RCT) in patients with completely resected stages II and IIIa NSCLC. Overall survival was estimated using the Kaplan-Meier method and compared via the log-rank test. Cox models were used to assess the impact of covariates on outcomes. Among 152 patients with assessable samples, 24 (16%) had NQO1*2. Median follow-up was 139 months. The presence of NQO1*2/*2 was associated with decreased overall survival (OS) (median in the heterozygote/wild-type group 42.3 vs. 33.5 months in the variant group, p=0.04). In a multivariable Cox model, variant NQO1 (HR = 1.58, p = 0.05), age <60 (HR = 0.67, p = 0.04), PS 1 (HR = 1.47, p = 0.05), cardiovascular disease (HR = 1.93, p = 0.003) and alkaline phosphatase <100 mg/ml (HR = 0.59, p = 0.005) were all significant predictors of OS. NQO1*2/*2 may be an independent predictor of poor overall survival in individuals with resected stages II and IIIa NSCLC. Although the basis for the NQO1 association with decreased survival requires additional evaluation, NQO1 may represent a biomarker for guiding individualized therapy.     

Facilitating online support groups for cancer patients: the learning experience of psycho‐oncology clinicians

Objective: Counsellor familiarity and engagement with technology‐mediated communication represents an important factor in the ability to implement support programs to cancer patients. This study describes the experiences of a cohort of expert psycho‐oncology counsellors who learned to facilitate online support groups (OSGs) and identifies the important elements of their learning experience that led to their engagement. Procedure and method: Six psycho‐oncology counsellors were trained to facilitate OSGs and later facilitated OSGs in their own practice context. They subsequently reflected on and discussed their experiences with OSGs over time: in a panel discussion within 6 months of training, and in two focus groups. A participatory method was used to describe and interpret key elements of the learning process. Results and discussion: Three themes of the counsellors' learning experience emerged: immersion in experiential learning, perceptions of clinical value and benefit, and overcoming challenges with adapted skills. Counsellors described components of their experiential learning: co‐facilitating online cancer support groups with an expert, debriefing online, and participating in an online peer supervision group, as critical to their becoming engaged. Despite initial challenges, the counsellors learned new skills, and adapted known clinical skills, to the text‐only environment. Conclusion: With appropriate training and practice over time, counsellors familiar with delivering face‐to‐face support groups to cancer patients became skilled and engaged in leading OSG's for cancer patients. Learning to facilitate OSGs shifted practice by significantly expanding the scope of services they were able to provide their patients and has implications for expanding access to support services. Copyright © 2010 John Wiley & Sons, Ltd.