Sunday, April 07, 2013
The Supreme Court should invalidate the patent on human DNA - The Washington Post
Article
"....the Supreme Court has a chance to rectify this genetic injustice. The justices will hear oral argument April 15 over a lower federal court’s decision that human genes can be patented. The case involves Myriad Genetics, which received patents in the 1990s for the exclusive right to examine any isolated DNA that contains the BRCA1 and BRCA2 genes.....
".....Like many scientists, we believe that these patents never should have been granted and that the genes of the human genome, like other natural body parts, belong to their owners, not to companies seeking to exploit monopolies. If the court allows these types of patents to stand, it will put the endeavors of openly researching, preventing and treating lethal diseases on a lower level of importance than a set of ill-conceived property rights.
Because of Myriad’s patents, any American who wants to have his or her DNA tested for the potentially life-threatening BRCA mutations has to use the services of Myriad Genetics. There is no possibility of an independent test. Myriad charges about $3,000 for the testing, but hundreds of clinical laboratories nationwide could do it for less than $200......
Characteristics of Opioid-Users Whose Death Was Related to Opioid-Toxicity
open access
Background
The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity.Results
Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359). Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer.Non-medical use of prescription opioids has culminated in a public health crisis in many North American jurisdictions. The impact of this crisis has been powerfully illustrated by the dramatic increase in opioid-related deaths [1]–[6]: in 2008, prescription opioids were involved in 14,800 accidental deaths in the United States [4]. That there has been a parallel increase in the consumption of prescription opioids and deaths related to opioid drugs is not in dispute......
Genetically modified foods, cancer, and diet: myths and reality
Blogger's Note: debates continue over genetically modified foods; acknowledging the pro's/con's it is (also) important to understand the issues for those countries who suffer from food security
Article
INTRODUCTION
This
commentary deconstructs, discredits, and demystifies the paradigm that
eating genetically modified foods causes cancer, and appraises the
research protocols needed to substantiate claims for cancer therapy.
CONCLUDING REMARKS
Avoiding gmfs
will neither stop nor prevent carcinogenesis. Healthy eating from
modern mass food production demands informed choice to realize the full
benefits of nutrition and to eschew co-factors for cancer. Vaccination
against known causes is desirable, and complementary therapies help to
palliate cancer morbidity. Scientists are free to express their ideas,
but they bear a responsibility to be objective and to provide a full,
open, rational, and transparent account of any research evidence
procured to substantiate their views.
That is no myth, it’s reality.
CONFLICT OF INTEREST DISCLOSURES
The author has no financial conflicts of interest to declareSaturday, April 06, 2013
open access - New perspectives on molecular targeted therapy in ovarian clear cell carcinoma
open access
There is now compelling evidence to suggest that epithelial ovarian cancers (EOCs) represent a heterogeneous group of tumours with distinct subtypes having different tissues of origin, molecular characteristics and outcome (Kurman and Shih, 2010). In Western populations, ovarian clear cell carcinomas (OCCCs) account for about 5–13% of all EOCs (Chan et al, 2008; McCluggage, 2008), whereas in Japan, its prevalence rises to 15–25% (Sugiyama et al, 2000; Itamochi et al, 2008) of all EOCs. It is currently unclear why OCCCs are more common in women of oriental descent, but, regardless of ethnicity, OCCCs have been shown to be associated with a poorer prognosis and are relatively resistant to conventional platinum-based chemotherapy when compared with other EOC subtypes (Tan and Kaye, 2007)......
"....These data suggest that OCCCs are genomically heterogeneous and that the pattern and complexity of genome-wide copy number aberrations are not only of taxonomic interest, but may also underpin the phenotypic differences in OCCCs with regard to clinical outcome. Indeed, it would appear that subgroups of OCCCs may harbour specific copy number changes that render them more chemoresistant than other OCCCs (Tan et al, 2011)......
Anticancer drugs might lead to bone metastasis, according to study
Article
"...While the compounds are currently being tested in Phase I and II trials, the authors are concerned that the long-term side effects of bone degradation and metastasis might not be noticed: Chang Yang, first author of the study, (Washington University School of Medicine) is wary that “these trials do not necessarily look for long-term effects of the drugs.” Continuing to explain this, Yang mentions that “if the cancer is going to metastasize to bone, it may take 6 months to 2 years to see that outcome. This may not be seen during the clinical trial.”....
Patents Associated with High-Cost Drugs in Australia
open access
"....Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators......
BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer
Abstract
The differentiation between hereditary and sporadic microsatellite-unstable (MSI-H) colorectal cancer is a crucial step in Lynch syndrome diagnostics. Within MSI-H colorectal cancers, the BRAF V600E mutation is strongly associated with sporadic origin.
Evolving concepts in the management of drug resistant ovarian cancer: Dose dense chemotherapy and the reversal of clinical platinum resistance
Abstract
"Despite
the initially high response rate to standard front-line debulking
surgery followed by platinum-based chemotherapy, the relapse rate in
ovarian cancer is high and many patients will recur within 6 months of
completing platinum based treatment. These patients may still require
further chemotherapy despite being considered “platinum resistant”. In
this setting, response rates to conventionally scheduled second line
platinum and non-platinum agents is low, ranging between 5% and 15%.
There is an emerging body of evidence that in this scenario,
chemotherapeutic activity can be enhanced using unconventionally
scheduled “dose-dense” platinum and non-platinum based regimens with
improved response rates of up to 65%. Randomised studies to evaluate the
impact of this approach on survival in recurrent, platinum resistant
disease are urgently required to confirm the promising phase II findings
if there is to be a change in the standard of care of patients with
platinum resistant disease. In this review we discuss the evolving
strategies to overcome resistance in patients with platinum resistant
ovarian cancer with a particular focus on alterations in dose schedule
as a means of reversing platinum resistance."
Friday, April 05, 2013
(2012) Immunoexpression and prognostic role of p53 in different subtypes of epithelial ovarian carcinoma
Abstract
"We sought to investigate the significance of p53 expression for epithelial ovarian
carcinoma. In this study, we used immunohistochemical method to
investigate the expression patterns of p53 in different subtypes of
epithelial ovarian carcinoma. We found that the expressions of p53 protein in epithelial ovarian cancer (pituita, serosity and intima) were 88.9%, 75% and 100%, respectively, while the recurrence rates among three cancer
subtypes were significantly different (33.3%, 12.5% and 0%,
respectively; P < 0.05). Compared with patients without lymph node
metastasis, the expression of p53 in patients with lymph node metastasis
was significantly strong (68.75% and 100%, respectively; P < 0.05).
However, the recurrence rate in the patients with lymph node metastasis
(40%) was higher than that without lymph node metastasis (6.25%, P <
0.05). The expressions of p53 protein in ovarian cancer
between I-II (25%) stage and II-IV stage (100%) were significantly
different (P < 0.05), and the recurrence rates between the two groups
were significantly different (0% and 31.25%, respectively, P <
0.05). Therefore, p53 protein has an intimate relationship with the
malignant degree and the prognosis of ovarian cancer."
Discovery Analysis of TCGA Data Reveals Association between Germline Genotype and Survival in Ovarian Cancer Patients
open access
Conclusions
"Discovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies......PLOS ONE: Expression of the Glioma-Associated Oncogene Homolog 1 (Gli1) in Advanced Serous Ovarian Cancer Is Associated with Unfavorable Overall Survival
open access
"Recent evidence links aberrant activation of Hedgehog (Hh) signaling with the pathogenesis of several cancers including medulloblastoma, glioblastoma, melanoma as well as pancreas, colorectal, and prostate carcinomas. Here we investigated the role of the transcription factor Gli1 in ovarian cancer. To this end, the expression profile of Gli1 was examined in normal ovaries, ovarian tumors, and ovarian cancer cell lines, and the in vitro effects of a specific Hh-pathway blocker, KAAD-cyclopamine, or a specific Gli1 inhibitor (GANT58) on cell proliferation and on Hh target gene expression were also assessed. Results obtained showed that epithelial cells in ovarian cancer tissue express significantly higher levels of nuclear Gli1 than in normal ovarian tissue, where the protein was almost undetectable.....
Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study
Abstract
Objective
To assess the influence of infertility and fertility drugs on risk of ovarian tumors.Design
Case-control study (Mayo Clinic Ovarian Cancer Study).Setting
Ongoing academic study of ovarian cancer.Patient(s)
A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use.Intervention(s)
None.Main Outcome Measure(s)
Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders.Result(s)
Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors.Conclusion(s)
We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation.Risk-Reducing Appendectomy and the Elimination of BRCA1 -Associated Intraperitoneal CancerRisk-Reducing Appendectomy in BRCA1 Carriers
JAMA - abstract
Risk-reducing bilateral salpingo-oophorectomy (RRBSO) and risk-reducing mastectomy are widely used for BRCA1 and BRCA2 mutation carriers to reduce the risk of ovarian and breast cancer. To our knowledge, no risk-reduction therapy has addressed the BCRA1/2 carrier lifetime risk of intra-abdominal peritoneal carcinoma from an appendix source. We identified a BRCA1 carrier in a hereditary breast and ovarian cancer kindred who developed a low-grade malignant appendiceal mucocele 2 years after risk-reducing salpingo-oophorectomy. Our retrospective meta-analysis assessed the risk of intraperitoneal appendiceal cancer in BRCA1/2 carriers after RRBSO to determine whether elective risk-reduction appendectomy could reduce the incidence of intraperitoneal cancer. Data sources included the case report and 12 reports of BRCA1 and BRCA2 carriers after RRBSO with ovarian, fallopian tube, breast, and peritoneal cancer published from January 1, 1985, through April 30, 2012. Main outcome measures were nonovarian, non–fallopian tube, nonbreast, positive intra-abdominal peritoneal carcinoma in previously cancer-free BRCA1/2 carriers after RRBSO. The source of intraperitoneal cancer in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy is highly likely the appendix. Use of risk-reduction appendectomy with RRBSO in younger BRCA1/2 carriers may reduce lifetime risk of malignant tumor and eliminate intraperitoneal cancer.
Countercurrents: Editorial - A new kind of breast / ovarian cancer gene mutation | Narod | Current Oncology
Article
S.A. Narod , MD
doi: http://dx.doi.org/10.3747/co.20.1403
" So, is it helpful to add PPM1D to the growing panel of ovarian cancer susceptibility genes?"
"A fascinating article, recently published in
Nature
and titled “Mosaic
PPM1D
Mutations Are Associated with Predisposition to Breast and Ovarian Cancer” by Nazneen Rahman and her colleagues1, is a rare example of a discovery that causes a re-evaluation of our assumptions about cancer and cancer genes.
The authors set out along a path well-travelled,
intending to look for rare but highly penetrant gene mutations that
might help to explain some of the residual heritability in breast and
ovarian cancer—that is, to explain cancer families without a
BRCA
mutation. They used next-generation sequencing to study a panel of 507 genes connected in some shape or form to
dna
repair. The experiment was an extension of earlier work, made
possible by the new technology. The project was facilitated by the
collection of 13,462
dna
samples from many patients over many years (attesting to the
prescience of the British funding authorities; I suspect that this
particular experiment was never detailed in full in a grant proposal)........
"In the analysis, one gene stood out:
PPM1D
(p53-inducible protein phosphate) outranked all the others by sheer statistical force. A
PPM1D
mutation was found in 18 of 6912 women with breast cancer, in 12 of
1121 women with ovarian cancer, but in only 1 of 5861 control subjects...........First, from a clinical point of view, the risk for ovarian cancer with
PPM1D
mutation (although not precisely known) looks to be as high as that
determined for any risk factor or gene mutation yet discovered. The
lifetime risk for a mutation carrier exceeds 60%, and so a preventive
oophorectomy is in order. The
PPM1D
gene appears to be responsible for about 1% of ovarian cancers—fewer than
BRCA1
or
BRCA2,
but comparable to the mismatch repair genes,
RAD51C
and
RAD51D.
The clinical scenario is much different, however......
Many mosaic mutations | Foulkes | Current Oncology
article
"Steven Narod’s latest Countercurrents contribution to
Current Oncology
discusses a new breast and ovarian cancer susceptibility gene known as
PPM1D
1. In this accompanying editorial, we put this exciting new finding in context.
MOSAICISM: WHAT IS IT AND HOW DOES IT HAPPEN?
Genetic mosaicism, as the name implies, indicates that the person is a
mosaic—that is, composed of more than one genotype. At the time of
diagnosis, all cancer patients are mosaics. They are mosaics because
they comprise at least two distinct genomes: the genome they were born
with, and the genome that they unwillingly acquired as a result of the
initiation and growth of cancer. In fact, as discussed next, it may be
that all humans are mosaics—but that some of us are more mosaic than
others......
media: Ontario wants independent probe into diluted cancer drugs
media
TORONTO - "Ontario will appoint an independent third party to review how watered down chemotherapy drugs were given to more than 1,100 patients, some for as long as a year, Premier Kathleen Wynne said Thursday. “It’s unacceptable that this should have happened, that the doses would not have been accurate,” said Wynne (premier of province).....
" The five hospitals are contacting affected patients to arrange quick appointments with their oncologists. Family members of Ontario patients who died are also being contacted."
"Health Canada, the provincial governments, Cancer Care Ontario and the Ontario College of Pharmacists are investigating. The hospitals are also conducting their own probes."
"Since hospitals buy the drugs, Cancer Care Ontario (Sawka) doesn’t know how many of them mix the drugs themselves or have it done off site, she said."
'" The supplier, Marchese Hospital Solutions, suggested the problem wasn’t how the drugs were prepared, but how they were administered at the hospitals."
Research Recruitment Practices of Critically Ill Patients: A Multicenter, Cross-Sectional Study (The Consent Study)
Abstract
Critical Care Medicine, St. Michael's Hospital, Toronto, Canada, Toronto, Canada.
RATIONALE:
Limited cross-sectional data exist to characterize the challenges of enrolling critically ill patients into research studies.OBJECTIVES:
We aimed to describe recruitment practices, document factors that impact recruitment, and identify factors that may enhance future research feasibility.METHODS:
We conducted a prospective, observational study of all critically ill adults eligible to participate in research studies at 23 Canadian intensive care units (ICUs). We characterized eligibility events into one of five consent outcomes, identified reasons why opportunities to recruit were missed or infeasible, and documented decision-maker's rationale for providing or declining consent.MEASUREMENTS AND MAIN RESULTS:
Only 8.9% of eligible patients made decisions for themselves.An International Assessment of Ovarian Cancer Incidence and Mortality
Conclusions
Ovarian
cancer survival has shown modest improvement from a statistical
perspective in the U.S. However, it is difficult to ascertain how
clinically relevant these improvements are at the population or patient
level.
Highlights
- •
- We assessed the global epidemiology of ovarian cancer and examined changes in worldwide incidence and mortality.
- •
- There was a modest decrease in incidence and significant increases in 12-, 24-, and 60-month survival in the US.
- •
- There is wide variation in the worldwide incidence of ovarian cancer, with the lowest rates consistently in China.
Objective
To
assess and characterize the temporal variation in ovarian cancer
incidence and mortality by age within countries in the Americas, Europe,
and Asia.
Methods/Materials
Data
from the National Cancer Institute’s Surveillance, Epidemiology, and
End Results Program in the United States (U.S.) were used to assess
ovarian cancer incidence rates (1998−2008) and mortality rates,
(1988−2007 for 12-month survival, 1988−2006 for 24-month survival, and
1988−2003 for 60-month survival), stratified by age at diagnosis. Data
from GLOBOCAN (link = 2008 data)were used to calculate country-specific incidence rates
for 2010 and 2020 and case-fatality rates for 2010.
Results
A
statistically significant decrease in Annual Percent Change (APC) of
ovarian cancer incidence was observed in the U.S. for all women
(-1.03%), among women who were diagnosed at < 65 years of age
(-1.09%) and among women who were diagnosed at ≥ 65 years of age
(-0.95%). There was a statistically significant increase in the observed
APC for survival at 12-months (0.19%), 24-months (0.58%), and 60-months
(0.72%) for all women; however, 5-year survival for advanced stage (III
or IV) disease was low at less than 50% for women < 65 years and
less than 30% for women ≥ 65 years. Global results showed a wide range
in ovarian cancer incidence rates, with China exhibiting the lowest
rates and the Russian Federation and the United Kingdom exhibiting the
highest rates.
Conclusions
Ovarian
cancer survival has shown modest improvement from a statistical
perspective in the U.S. However, it is difficult to ascertain how
clinically relevant these improvements are at the population or patient
level.
Obstetrics and Gynecology Practices and Patient Insurance Type
Blogger's Note: the abstract does not indicate if cancer screening specifically was part of the study; however, given the number of women who are not referred to a gyn/onc, if it wasn't it should have been - assumption based on limited information in abstract
Abstract
Background
Despite
research on health disparities based on insurance status, little is
known about the differences in practice patterns among physicians who
cater to privately and non-privately insured patients. The aim of this
study was to assess how obstetrician–gynecologists (ob-gyns) who
primarily see patients with private insurance differ from those who see
mainly uninsured or publicly insured patients. This could be informative
of the needs of these two groups of physicians and patients.
Methods
A
questionnaire was mailed or emailed to 1,000 members of the American
College of Obstetricians and Gynecologists, 600 of whom participate in
the Collaborative Ambulatory Research Network.
Findings
A
56.4% response rate was obtained. Of the valid responders, the 335
reported providing care to a majority of patients with private insurance
(“private group”) and the 105 reported providing care to mostly
publicly insured or uninsured patients (“non-private group”) were
included in our analyses. Differences between groups included that the
private group was more likely to see patients before their becoming
pregnant and spent more time on well-woman care. The private group was
more likely to see patients who are White, Asian, or between the ages of
45 and 64. The non-private group was more likely to see Hispanic
patients and those under age 18.
Conclusion
Results
reveal that ob-gyns who see mostly privately insured patients have
different clinical experiences than those who see mainly uninsured or
publicly insured patients in terms of patient characteristics,
preconception care, distribution of time on activities, and the of
likelihood performing certain procedures and screening tests.
Secondary debulking surgery in ovarian cancer patients with isolated nodal recurrence located in the region above and behind the renal vein
Abstract
Objective
We
describe our early experience with a suprarenal and retrorenal
para-aortic lymphadenectomy involving the mobilization of the left
kidney.
Methods
Three patients
with isolated nodal recurrence located in the region above and behind
the renal vein underwent the removal of these metastatic lymph nodes
using a left renal mobilization procedure.
Results and Conclusion
The
enlarged suprarenal and retrorenal lymph nodes were safely and
effectively removed in all 3 patients. Postoperatively, a lymphatic
fistula developed in one patient. However, no morbidities related to
renal mobilization, including renal ischemia, were observed in the
current series. A further large, prospective study is required to
evaluate this surgical procedure.
Folate Receptor Alpha (FRA) Expression Remains Unchanged in Epithelial Ovarian and Endometrial Cancer after Chemotherapy
Abstract
Highlights
- •
- Both epithelial ovarian and endometrial cancer demonstrate high expression of FRA (folate receptor alpha) compared to normal ovarian and endometrial tissue
- •
- FRA expression is not altered by chemotherapy exposure at interval debulking surgery nor at recurrence
- •
- Immunohistochemical FRA staining at diagnosis can guide the decision whether to use FRA targeted therapy upon recurrence
Objective
Based
on its expression profile, folate receptor alpha (FRA) is an attractive
candidate for targeted diagnostics and therapeutics. However,
applicability of these agents in residual or recurrent disease could be
influenced by chemotherapy. We evaluated whether chemotherapy modified
FRA expression in non-mucinous epithelial ovarian (EOC) and endometrial
carcinoma (EC).
Ovarian surface epithelium as a source of ovarian cancers: Unwarranted speculation or evidence-based hypothesis? (serous)
Abstract
Highlights
- •
- Pure cultures of ovarian surface epithelium (OSE) can be transformed tor high and low grade serous carcinomas.
- •
- OSE-lined inclusion cysts undergoing morphologic and functional serous metaplasia show intermediate transitional stages, thus ruling out implants from fimbrial epithelium.
- •
- Caltretinin and PAX8 are not reliable markers to determine the origin of epithelial inclusion cysts as either OSE or fimbriae.
Objectives
There
has been increasing evidence that high grade serous ovarian carcinomas
(HGSOCs), the most common and most lethal of all ovarian cancers,
originate in oviductal fimbriae and metastasize to the ovary. The
alternate hypothesis, that ovarian carcinomas may originate within the
ovarian stroma in inclusion cysts lined by ovarian surface epithelium
(OSE), has been criticized and often dismissed on the basis of the OSE’s
embryonic origin, mesothelial phenotype, tissue-specific markers,
questionable ability to undergo metaplasia, and the lack of identifiable
precursor lesions. This review analyses these criticisms and summarizes
evidence indicating that OSE as a source of ovarian cancers cannot be
ruled out.
Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: Primum Non Nocere
Abstract
Highlights
- •
- Ovarian function is not compromised by adding bilateral salpingectomy to TLH ( total laparoscopic hysterectomy (TLH) )
- •
- Laparoscopic bilateral salpingectomy is a safe procedure when added to TLH
- •
- Premenopausal prophylactic salpingectomy is a safe procedure for preventing HGSC
Objective
The
objective of this study is to compare ovarian function and surgical
outcomes between patients affected by benign uterine pathologies
submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy
and women in which standard TLH with adnexal preservation was performed.
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