Wednesday, June 16, 2010
Note: interesting article
"A University of Edinburgh study suggests that ovarian cancer patients whose tumours spread to the solid organs such as the liver and lungs should be tested for the faulty genes - BRCA1 and BRCA2 - to ensure they are given the most appropriate treatment...."
full free access: Biomarkers in Medicine - The dire need to develop a clinically validated screening method for the detection of early-stage ovarian
Note: I remember the LPA very well (breakthrough screening test for ovarian cancer and the resulting media hype extraordinaire)
Multiple initiatives have been undertaken to discover strategies that detect and diagnose early-stage EOC, including the search for novel serum biomarkers and the development of new technologies, such as contrast-enhanced ultrasonography, with a number of them demonstrating hopeful results. The ideal screening test for ovarian cancer would be a simple measurement of biomolecules in bodily fluids, such as blood, serum or urine, whose absolute concentrations could differentiate cancer from noncancer and be organ specific. In the last decade, insights into the EOC microenvironment, as well as technological advances, such as microarrays and proteomics, have triggered the discovery of hundreds of potential clinically valuable biomarkers:
▪ Lysophosphatidic acid (LPA) is a phospholipid derivative consisting of a glycerol backbone, a single fatty acid chain and a free phosphate group. LPA has a variety of isoforms depending on fatty acid-chain variability at the sn-1 position. LPA was found to be elevated in the serum, plasma and malignant effusions of women with ovarian cancer and has known functions in cell proliferation, invasion and angiogenesis . This molecule initially became of interest in 1998 for its reported high sensitivity and specificity to detect early-stage ovarian cancer ; however, its utility as a screening biomarker has been limited owing to the difficulty of isolating and detecting the different isoforms in patients’ serum and its specificity for ovarian cancer;
▪ Human epididymal protein (HE)4 is a relatively new biomarker used to monitor disease recurrence and disease progression in patients with ovarian cancer. It is the product of the WFDC2 (HE4) gene, which is overexpressed in ovarian cancer. HE4 has exhibited increased sensitivity to detect stage I disease  and has demonstrated promise as a sensitive and specific biomarker when combined with CA125 and other molecules ; although, more studies remain to be done to warrant its use as a biomarker for the detection of early-stage EOC;
▪ Osteopontin (OPN) is a glycoprotein involved in cell adhesion, inflammation and tumorigenesis, with elevated levels seen in ovarian cancer . Similar to HE4, OPN has been used in combination assays to identify ovarian cancer ; however, OPN is also elevated in other cancers and benign conditions, limiting its specificity to be used as an ovarian cancer biomarker;
▪ Kallikreins (KLKs) are serine proteases that function in cell growth, angiogenesis and invasion. KLKs are elevated in patient serum with ovarian cancer. KLK8 was reported to be associated with early disease, while KLK5, -6, -10 and -13 have been combined with CA125 to improve the accuracy of ovarian cancer detection [8,9];
▪ Claudins are components of tight junctions that create selective barriers and maintain cell polarity. Multiple claudins have been found to be elevated in ovarian cancer; however, their specificity has yet to be determined and verified .
Of particular note, traditional genetic pedigree analysis of ovarian cancer patients may provide information to help identify high-risk populations; for example, inherited BRCA1 and -2 mutations increase the risk for women to develop ovarian and/or breast cancer . In addition, molecular profiling at the epigenetic level, such as miRNA profiling, may allow for the identification of novel biomarkers for early detection of ovarian cancer, given that these epigenetic changes might be detectable before the development of the physical tumor.
Despite these advances, at present, no clinically validated screening protocol for the detection of early-stage EOC exists. The discovery of novel biomarkers relies on obtaining a better understanding of the initiation and progression of EOC. Clinical validation and implementation of biomarkers will also benefit from advancements in new molecular and imaging technologies as patient care is optimized. Fortunately, hundreds of biomarkers have been identified; however, their clinical utility remains to be determined. In addition, the enhanced imaging capabilities of the ovary by ultrasound are providing practitioners with the ability to more accurately and precisely identify changes specific to the newly transformed ovary. The combination of these two modalities, biomarker panels and biologically based imaging may be the future. Therefore, we must forge ahead to develop a validated early-detection protocol that will not only decrease the number of advanced-stage diagnoses and deaths attributed to ovarian cancer but, most importantly, positively impact the future of women’s healthcare.
Ovarian Low Malignant Potential Tumors (borderline ovarian tumors) Treatment, Masonic Cancer Center, University of Minnesota
Note: also commonly referred to as "LMP"
Monday, June 21
Endocrine-Disrupting Chemicals: Evidence of Impact (9:30 a.m. PDT): Frontier research on the impact of exposure to endocrine-disrupting chemicals.
Menopause: Hormones and the Aging Woman (1:30 p.m. PDT): Release of the Society’s scientific statement on postmenopausal hormone therapy and breaking research on risks associated with menopause and treatment of menopausal symptoms.
Note: excerpt - Avastin + chemo
"Genentech and Roche are also conducting a randomized double-blind placebo-controlled Phase II trial in advanced ovarian cancer in a maintenance setting, which is evaluating the ability of GDC-0449 to slow the time to recurrence of cancer in patients whose disease is in complete remission, by impeding the residual cancer cells' ability to grow. Roche has indicated that results from this study are expected during the second half of 2010."
A prime example of the problem with some TV physician-"journalists" - Gary Schwitzer's HealthNewsReview Blog (ASCO/ovarian cancer/Avastin) + my response
Note: my response:
"In our own ovarian cancer patient communities and over the long term, as survivours/family caregivers, many of us have learned to question media articles and abstracts. The SGO published a statement regarding the GOG 218 study shortly after the media events.
In addition, on June 5th in Chicago on a separate ovarian cancer seminar the issue of the new finding of GOG 218 were discussed. The over-riding bottom line is that Avastin is not the panacea for all that ails ovarian cancer women and should be used very selectively. On which patients is of primary interest (obviously).
The issue at stake for ovarian cancer women is that no new treatments in the past 2 decades have shown any improvements over the standard and current first line therapy of Taxol and Carboplatin.
No matter how bad it gets (QOL) and it does get very 'bad', ovarian cancer women want to live and will suffer much to do so. We need to understand this mindset while at the same time considering first most patient safety and always acknowledging the 'hype'.
There is a duty for all those who care for ovarian cancer women to be informed.
Twitter, blogs, facebook and social media help also to educate patients on these issues - we hope."
(The Patient Factor) - Patient Safety (Canada) - patient advocacy/system - illustrated by Ed Mendoza's journey on behalf and for his wife
"....In February 2008 he sat on the steering committee of PFPSC and helped them develop a charter for the organization. Three months later the amicable relationship between Ed and the WRHA ended abruptly when they informed him that a restructuring of their Patient Advisory Council meant that he could no longer be a member. Ed was extremely disappointed but undeterred in his patient safety efforts. In September 2008 the CPSI, the funding body for PFPSC, invited him to speak at their Canadian Patient Safety Officer Course. One month later he received a call from PFPSC dismissing him from the group. In January 2009 he received an official letter outlining the reason for his expulsion. The letter makes reference to his speaking engagement and the message contained in his information booklet...."
Abstract (in research)
"Recent studies have demonstrated overexpression of osteopontin (OPN) in ovarian clear cell carcinoma.
Here, we revealed the role of OPN in invasiveness in ovarian clear cell carcinoma......Immunofluorescence analysis revealed statistically significant differences among the histological groups, and ovarian clear cell carcinoma expressed a strong OPN signal....Simvastatin significantly reduced expression of OPN and the integrins, and decreased ECM invasion. RNA interference also suppressed ECM invasion....We thus conclude that OPN regulation could have a crucial role in ovarian clear cell carcinoma therapy."
Note: including my comment (see article); old and outstanding issues/dialogue anyone?
".....Last weekend I was part of a group working on a conference for cancer patients. There were no patients listed as conference speakers ........."
The primary care physician role in cancer genetics: a qualitative study of patient experience Family Practice
Background. Increased availability of genetic testing is changing the primary care role in cancer genetics. The perspective of primary care physicians (PCPs) regarding their role in support of genetic testing has been explored, but little is known about the expectations of patients or the PCP role once genetic test results are received.
Methods. Two sets of open-ended semi-structured interviews were completed with patients (N = 25) in a cancer genetic programme in Ontario, Canada, within 4 months of receiving genetic test results and 1 year later; written reports of test results were collected.
Results. Patients expected PCPs to play a role in referral for genetic testing; they hoped that PCPs would have sufficient knowledge to appreciate familial risk and supportive attitudes towards genetic testing. Patients had more difficulty in identifying a PCP role following receipt of genetic test results; cancer patients in particular emphasized this as a role for cancer specialists. Still, some patients anticipated an ongoing PCP role comprising risk-appropriate surveillance or reassurance, especially as specialist care diminished. These expectations were complicated by occasional confusion regarding the ongoing care appropriate to genetic test results.
Conclusions. The potential PCP role in cancer genetics is quite broad. Patients expect PCPs to play a role in risk identification and genetics referral. In addition, some patients anticipated an ongoing role for their PCPs after receiving genetic test results. Sustained efforts will be needed to support PCPs in this expansive role if best use is to be made of investments in cancer genetic services.