Wednesday, April 25, 2012
open access: Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis (ovarian/GI tract cancers)
Cell–cell and cell–matrix dynamics in intraperitonealcancer metastasis
Abstract/pdf full text:
IntroductionIntraperitoneal dissemination is the primary metastatic route
of ovarian cancers. It is also a common progression for
gastrointestinal malignancies including colorectal, gastric,
and pancreatic cancers.....
~~~~~~~~~~~~~~~~~
The peritoneal metastatic route of cancer dissemination
is shared by cancers of the ovary and gastrointestinal
tract. Once initiated, peritoneal metastasis typically proceeds
rapidly in a feed-forward manner. Several factors
contribute to this efficient progression. In peritoneal metastasis,
cancer cells exfoliate into the peritoneal fluid and
spread locally, transported by peritoneal fluid. Inflammatory
cytokines released by tumor and immune cells compromise
the protective, anti-adhesive mesothelial cell layer that lines
the peritoneal cavity, exposing the underlying extracellular
matrix to which cancer cells readily attach. The peritoneum
is further rendered receptive to metastatic implantation and
growth by myofibroblastic cell behaviors also stimulated by
inflammatory cytokines. Individual cancer cells suspended
in peritoneal fluid can aggregate to form multicellular spheroids.
paywalled: Emergency department visits for symptoms experienced by oncology patients: a systematic review
Emergency department visits for symptoms... [Support Care Cancer. 2012] - PubMed - NCBI
CONCLUSIONS:
Individuals with cancer present to emergency departments with a myriad of symptoms. Over half of emergency department visits resulted in hospital admissions. Few symptoms were defined adequately to compare data across studies, thereby revealing an important gap in cancer symptom reporting.paywalled: Cancer Risks for Relatives of Patients With Serrated Polyposis : The American Journal of Gastroenterology + link to Johns Hopkins (further explanation/genetics)
Access : Cancer Risks for Relatives of Patients With Serrated Polyposis : The American Journal of Gastroenterology
CONCLUSIONS:
Our finding that
relatives of serrated polyposis patients are at significantly increased
risk of colorectal and pancreatic cancer adds to the accumulating
evidence that serrated polyposis has an inherited component.
~~~~~~~~~~~~~~~~~
Johns Hopkins Colon Cancer Center:
Individuals are diagnosed with hyperplastic polyposis when they have multiple hyperplastic polyps, usually greater than 20 polyps. The number of polyps ranges anywhere from 6 to greater than 100, though most individuals with hyperplastic polyposis have between 40 and 100 polyps. A diagnosis of Hyperplastic polyposis may also made in individuals who present with fewer than 20 hyperplastic polyps, but whose polyps are larger, often greater than 2 centimeters. Individuals may also be diagnosed with multiple serrated adenomas or a mix of both serrated adenomas and hyperplastic polyps. Hyperplastic polyposis is usually diagnosed in individuals in their 40’s to 60’s, though it has been reported in individuals as young as 11 years old. Individuals with hyperplastic polyposis are at an increased risk for developing colorectal cancer, so routine screening is extremely important. Although the genetic basis for FAP, HNPCC, Peutz-Jeghers, MYH-Associated Polyposis, and juvenile polyposis has been identified, hyperplastic polyposis has not yet been explained. Hyperplastic polyposis is suspected to have a familial basis and reports have shown that is inheritable in 5% of cases, though the exact mechanism of inheritance has not been identified.
Supplements and cancer prevention: A cautionary tale - Journal of National Cancer Institute - press release
Supplements and cancer prevention: A cautionary tale
Public release date: 25-Apr-2012
Journal of the National Cancer Institute
Supplements and cancer prevention: A cautionary tale
Government regulators and the scientific community should work to ensure that they give clear guidance to the public about dietary supplements and cancer risk, according to a commentary published April 25 in the Journal of the National Cancer Institute.Evidence from animal, in vitro and observational studies has suggested that taking dietary supplements may lower cancer risk. However, the small number of randomized controlled studies, the gold standard in evidence-based medicine, has not confirmed this—and some studies have actually shown that supplements may increase cancer risk. Still, the supplement industry is booming, with estimated annual sales at $30 billion in the U.S.
To examine the potential role of dietary supplements and cancer risk, Maria Elena Martinez, Ph.D., of the University of California San Diego Moores Cancer Center and colleagues, looked at observational studies of several supplements, including anti-oxidants, folic acid, vitamin D, and calcium. Several observational studies found that diets high in fruits and vegetables were associated with lower risk of certain cancers, including respiratory and gastrointestinal. Specifically, with respect to anti-oxidant supplements, the authors found that: "The importance of oxidative stress for carcinogenesis does not establish that the administration of supplemental antioxidants will protect against the carcinogenesis that oxidative stress may induce." Furthermore, they write, "Supplementation by exogenous antioxidants may well be a two-edged sword; these compounds could, in vivo, serve as pro-oxidants or interfere with any of a number of protective processes such as apoptosis induction." Indeed, several antioxidant trials the researchers examined reported increased cancer risks with supplementation. They looked at trials with supplements using folic acid, vitamin D and calcium, among other compounds.
The researchers caution against taking dietary supplements for
cancer prevention, adding that many expert committees and organizations
have concluded that nutritional supplements have little or no benefit in
cancer prevention. They say that more randomized control
trials—spanning many years instead of just a few—are needed to verify
the effect of nutritional supplementation in cancer risk.
Add-on bevacizumab slows progression of recurrent ovarian cancer - - ModernMedicine
Add-on bevacizumab slows progression of recurrent ovarian cancer - - ModernMedicine
(from Reuters) "....Dr. Aghajanian and colleagues note that overall survival data from the trial are not yet available; information on clinicaltrials.gov indicates a predicted study completion date of October 2013.
For now, say the researchers, "The data from OCEANS demonstrate that the addition of BV (bevacizumab) to GC (gemcitabine and carboplatin) can improve outcomes, and ongoing studies will assess whether this ability to add benefit is universal to other platinum-based combinations."
OCEANS is supported by Genentech, which markets bevacizumab as Avastin.
Patient-Centered Outcomes Research Institute Amends Draft Research Agenda in Response to Public Comment -- WASHINGTON, April 25, 2012 /PRNewswire-USNewswire/ --
Patient-Centered Outcomes Research Institute Amends Draft Research Agenda in Response to Public Comment -- WASHINGTON, April 25, 2012 /PRNewswire-USNewswire/ --
".....After discussion, the Board voted to make important changes to the Research Agenda. These include clarification of PCORI's focus on patient engagement and transparency; on patients with multiple chronic conditions; on patients with rare diseases; on improving health care systems, including care coordination, access to care, and the role of practice settings and allied health professionals; and on the importance of health literacy.
"The comments we received did not identify major gaps in the National Priorities, and there were no suggestions for additional priorities," said PCORI Executive Director Joe Selby, M.D., MPH. "This indicates that our priorities effectively capture the broad areas where more research is needed. Once the revised National Priorities and Research Agenda are approved, we will issue PCORI's first primary research funding announcements, which will emphasize the inclusion of patients and caregivers at all stages of the research."
PCORI reiterated its commitment to being a learning organization that will continually work with patients and stakeholders to revise its priorities and agenda as needed to address patients' evolving needs....."
open access: Oxaliplatin-related thrombocytopenia
Oxaliplatin-related thrombocytopenia
Abstract/Full Text:
Oxaliplatin is a third generation platinum
compound that inhibits DNA synthesis, mainly through intrastrandal
cross-links
in DNA. Most of the experience with the clinical
use of this drug is derived from colorectal cancer but it is also used
in
other tumor types such as ovary, breast, liver and
non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen
during
oxaliplatin treatment, occurring at any grade in up
to 70 % of patients and leading to delays or even discontinuation of
the
chemotherapy. Although myelossupression is
recognized as the main cause of oxaliplatin-related thrombocytopenia,
new mechanisms
for this side-effect have emerged, including
splenic sequestration of platelets related to oxaliplatin-induced liver
damage
and immune thrombocytopenia. These new
pathophysiology pathways have different clinical presentations and
evolution and may
need specific therapeutic maneuvers. This article
attempts to review this topic and provides useful clinical information
for
the management of oxaliplatin-related
thrombocytopenia.
conclusions
Oxaliplatin-related thrombocytopenia can
prevent the administration of the optimal dose and schedule of this
important chemotherapy
agent and limit its benefits in the adjuvant or
metastatic setting. Mild to moderate bone marrow suppression is the main
cause
of thrombocytopenia during and after treatment with
oxaliplatin. In this setting, patients present thrombocytopenia
concomitant
to anemia and neutropenia usually 1–2 weeks after
treatment. Therapeutic approaches will include dose delays or reduction
and consideration of platelet-stimulating agents.
However, novel mechanisms of oxaliplatin-related thrombocytopenia should
promptly be recognized by physicians and include an
immune-dependent mechanism, as well as portal hypertension related to
sinusoidal injury yielding splenic sequestration of
platelets.
OIIT usually presents a sudden and
isolated drop in platelet counts minutes to hours after oxaliplatin
administration, leading
to acute hemorrhagic events. Female patients with
advanced CRC and prior oxaliplatin exposure are more likely to develop
this
consequence. Prompt immunological testing
documenting oxaliplatin-mediated platelet destruction leads to
definitive diagnosis.
Platelets counts will improve after discontinuation
of treatment and transfusions may be necessary during the acute phase.
Other measures such as corticoid or immunoglobulin
administration are controversial and patients with documented OIIT
should
not be rechallenged with oxaliplatin.
Hepatic sinusoidal injury is a well-known
complication of oxaliplatin treatment and can lead to portal
hypertension and hypersplenism.
Thrombocytopenia in this setting demonstrates a
different natural history, with moderate but prolonged reductions in
platelet
counts. Splenomegaly and other complications of
portal hypertension are recognized in these patients. Platelet recovery
is
slow and usually takes 2–3 years to be complete
after treatment discontinuation. When a fast platelet recovery is
wanted,
splenic embolization might be considered as a
therapeutic measure.
An improvement in the recognition of
these mechanisms of oxaliplatin-related thrombocytopenia will permit a
better documentation
of them and help to understand possible risk
factors associated with this complication in different settings. This
information
may help the development of new preventive and
therapeutic approaches and allow for a more rational management of
cancer patients
treated with oxaliplatin that present
thrombocytopenia.
paywalled: Japanese Journal of Clinical Oncology- LAPTM4B Polymorphisms is Associated with Ovarian Cancer Susceptibility and Its Prognosis
LAPTM4B Polymorphisms is Associated with Ovarian Cancer Susceptibility and Its Prognosis:
Objective
Lysosome-associated protein transmembrane 4 beta (LAPTM4B) is an important novel gene associated with the proliferation and differentiation of cells. Recent studies have shown that it was overexpressed in many cancer tissues. This study investigated the association between different LAPTM4B polymorphisms and the susceptibility and prognosis of ovarian cancer.
Methods
A case–control study was performed in 282 patients with ovarian cancer and 365 control subjects. Genomic DNA was extracted from peripheral blood lymphocytes in all participants. LAPTM4B genotypes were determined using polymerase chain reaction.
Results
There was a significantly higher LAPTM4B*2 allele frequency in ovarian cancer cases than controls (P < 0.05). Using the LAPTM4B*1/1 genotype as the reference, we found that the LAPTM4B*1/2 and LAPTM4B*2/2 genotypes were positively associated with ovarian cancer.
Current Drug Shortages: Paclitaxel Injection (updated)
Current Drug Shortages: Paclitaxel Injection (updated):
APP is currently back-ordered on 100 mg/16.7 mL vial (NDC 63323-0763-16) and 300 mg/50 mL vial (NDC 63323-0763-50). 30 mg/5 mL vial (NDC 63323-0763-05) is currently available.
Current Drug Shortages: Ondansetron Injection 2 mg/mL (updated)
Current Drug Shortages: Ondansetron Injection 2 mg/mL (updated):
APP has Ondansetron 2 mg/mL 2 mL vials on back order with an estimated release date of early May 2012. Check wholesalers for inventory. The 40 mg, 20mL vials are on back-order until late May.
paywalled: Jpn. J. Clin. Oncol. (2012) - Oncology Information on the Internet
Oncology Information on the Internet
Abstract:
Owing to new developments in Internet
technologies, the amount of available oncology information is growing.
Both patients
and caregivers are increasingly using the Internet
to obtain medical information. However, while it is easy to provide
information,
ensuring its quality is always a concern. Thus,
many instruments for evaluating the quality of health information have
been
created, each with its own advantages and
disadvantages. The increasing importance of online search engines such
as Google
warrants the examination of the correlation between
their rankings and medical quality. The Internet also mediates the
exchange
of information from one individual to another.
Mailing lists of advocate groups and social networking sites help spread
information
to patients and caregivers. While text messages are
still the main medium of communication, audio and video messages are
also
increasing rapidly, accelerating the communication
on the Internet. Future health information developments on the Internet
include merging patients' personal information on
the Internet with their traditional health records and facilitating the
interaction among patients, caregivers and
health-care providers. Through these developments, the Internet is
expected to
strengthen the mutually beneficial relationships
among all stakeholders in the field of medicine.
paywalled: Clinical development of new formulations of cytotoxics in so... : Current Opinion in Oncology
Clinical development of new formulations of cytotoxics in so... : Current Opinion in Oncology
Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 325–331
doi: 10.1097/CCO.0b013e328351fb29
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada
Clinical development of new formulations of cytotoxics in solid tumors
Purpose of review:
To discuss the clinical development
of new formulations of old cytotoxic agents and highlight the value of
adopting this strategy.
Recent findings:
Several drugs are currently in
clinical development with high potential in improving clinical outcomes
compared with their older counterparts. We emphasize on the results of
four of these agents, each belonging to a known group of cytotoxics
namely amrubicin, EndoTAG-1, pralatrexate and NKTR-102. Each has shown
promising results that have the potential in addressing some limitations
that have been observed with the ‘earlier generation’ agents.
Summary:
Improvement in drug development strategies
and the appreciation of the mechanisms of action and resistance of the
cytotoxic agents currently available in the clinic open the door for
developing agents that have the potential of improving clinical outcomes
with better safety profiles. It is important to adopt innovative
clinical trials designs integrating molecular markers in early clinical
development in order to identify the subgroups of patients who would
derive the maximal benefit of these novel agents.
paywalled: Targeting the DNA damage response in oncology: past, presen... : Current Opinion in Oncology
Targeting the DNA damage response in oncology: past, presen... : Current Opinion in Oncology
Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 316–324
doi: 10.1097/CCO.0b013e32835280c6
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada
Targeting the DNA damage response in oncology: past, present and future perspectives
Abstract
Purpose of review:
The success of poly(ADP-ribose)
polymerase inhibition in BRCA1 or BRCA2 deficient tumors as an
anticancer strategy provided proof-of-concept for a synthetic lethality
approach in oncology. There is therefore now active interest in
expanding this approach to include other agents targeting the DNA damage
response (DDR). We review lessons learnt from the development of
inhibitors against DNA damage response mechanisms and envision the
future of DNA repair inhibition in oncology.
paywalled: Vascular disrupting agents: a delicate balance between efficacy and side (safety) effects
Vascular disrupting agents: a delicate balance between effi... : Current Opinion in Oncology
Current Opinion in Oncology:
May 2012 - Volume 24 - Issue 3 - p 305–315
doi: 10.1097/CCO.0b013e32835249de
INNOVATIVE EARLY CLINICAL TRIALS METHODOLOGY AND NEW THERAPEUTICS IN CANCER: Edited by Ahmad Awada
Abstract
Purpose of review:
Targeting the tumor vasculature is
an attractive approach for cancer therapy. Vascular disrupting agents
(VDAs) are compounds that directly target tumor blood vessels and create
central tumor necrosis. The current review aims to summarize the
clinical development (i.e. safety and efficacy) of this class of
compounds.
Recent findings:
VDAs have demonstrated signs of
clinical activity in different tumor types [e.g. anaplastic thyroid
carcinoma (ATC), nonsmall cell lung carcinoma (NSCLC), ovarian cancer,
sarcoma]. However, the lack of predictive biomarkers to identify
patients with a high probability of response to VDAs, places this class
of compounds at a high risk of failure. This has recently been
exemplified by several negative phase II/III trials in NSCLC, ATC, and
castration-refractory metastatic prostate cancer.
Summary:
VDAs represent a unique class of anticancer
compounds. Their clinical development is hampered by cardiovascular,
neurological toxicities as single agent and by hematological toxicity in
combination with chemotherapy. Molecular predictors of their efficacy
are crucial for further development. As single agent, only few objective
responses have been observed in a variety of solid tumors. However,
VDAs have failed to demonstrate a survival advantage in several phase
II/III trials especially in combination with chemotherapy.
paywalled: ncreased risk of neoplasm in appendicitis treated w... [Am Surg. 2012] - PubMed - NCBI
Increased risk of neoplasm in appendicitis treated w... [Am Surg. 2012] - PubMed - NCBI
Am Surg. 2012 Mar;78(3):339-43.
Increased risk of neoplasm in appendicitis treated with interval appendectomy: single-institution experience and literature
Abstract
Appendicitis is a common diagnosis encountered by the acute care surgeon. Management of complicated appendicitis is controversial and often involves initial nonoperative therapy with interval appendectomy. This study reviews single-institutional experience with management of complicated appendicitis with interval appendectomy and addresses an unusually high occurrence of incidental appendiceal malignancies observed with a review of relevant literature. A retrospective review of all diagnoses of appendicitis was performed over 5 years at a tertiary care center. Patient demographics, time to surgery, operative technique, pathologic diagnosis, and clinical outcomes were examined. Three hundred fifteen patients were diagnosed with acute appendicitis. Of these, 24 (7.6%) were deemed complicated and did not undergo immediate appendectomy, and 18 ultimately underwent appendectomy at our institution and were included in analysis. There were no statistical demographic or symptomatic differences between the immediate and interval appendectomy patients. Ninety-nine per cent of the immediate appendectomy patients were treated laparoscopically; 78 per cent of the interval group underwent attempted laparoscopic treatment with 56 per cent completed without conversion to open (P < 0.01). Neoplasms were discovered in 1 per cent of the acute appendectomy group and 28 per cent of the interval appendectomy group (P < 0.0001). Two of the three neoplasms in the acute group were carcinoid, whereas three of the five neoplasms in the interval group were adenocarcinoma. Surgeons should consider appendiceal or colonic neoplasms in cases of complicated appendicitis when nonoperative management is considered. This is most important in patients older than 40 years, in those who forego interval appendectomy, or in those who could be lost to follow-up.paywalled: Breast cancer metastasising to the pelvis and abdomen: what the gynaecologist needs to know - 2012 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library
Breast cancer metastasising to the pelvis and abdomen: what the gynaecologist needs to know - Moore - 2012 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library
A
small proportion of breast cancers metastasize within the peritoneal
cavity. With increasing breast cancer incidence rates, gynaecologists
and oncologists will encounter such women more frequently. Most women
with intraperitoneal breast cancer are premenopausal. Although data are
limited and are likely to be subject to selection bias, the median
survival of women undergoing resection appears superior to those not
undergoing surgery. Furthermore, survival is broadly similar to that for
women undergoing advanced ovarian cancer surgery, particularly when
tumour debulking is optimal. Obtaining data via randomised trials is
unlikely to be feasible and therefore we recommend prospective data
collection via the establishment of an international intraperitoneal
breast cancer patient registry. For individual women where survival is
anticipated to be more than a few months, we suggest considering
referral to a gynaecological oncology team for discussion of surgical
options.
future postings - term 'subscription required' replaced by 'paywalled'
Blogger's Note: wording/term change - 'paywalled' (new) = subscription required ($$$) (old), plain english - blog postings of the future which indicate the term 'paywalled' means that access to the article requires a paid subscription
abstract: Topoisomerase 1 Inhibitors and Cancer Therapy
Blogger's Note: to view full paper, subscription ($$$) required
Topoisomerase 1 Inhibitors and Cancer Therapy
Abstract: "Topoisomerase 1 inhibitors cure human cancer xenografts in animal models, more so than most other chemotherapy agents. However, their activity in patients with cancer is modest. Ongoing research is studying the optimal analogues that could reproduce animal data in the cancer population. This article analyzes the clinical research with topoisomerase 1 inhibitors in ovarian cancer."
financial: Amgen - Media - Press Release (Product Sales Performance eg. Neupogen/Etanercept/Darbepoetin/Aranesp/Epogen...)
Amgen - Media - Press Release
Product Sales Performance
XGEVA® (denosumab) sales were $153 million in the first quarter of 2012, an increase of 14 percent over the fourth quarter of 2011, reflecting increased segment share as well as overall segment growth.
Prolia® (denosumab) sales were $88 million in the first quarter of 2012, an increase of 9 percent over the fourth quarter of 2011, reflecting continued global growth.
Combined Neulasta® (pegfilgrastim) and NEUPOGEN® (Filgrastim) sales increased 9 percent to $1,344 million in the first quarter of 2012 versus $1,232 million in the first quarter of 2011. Combined U.S. Neulasta and NEUPOGEN sales increased 13 percent to $1,053 million in the first quarter of 2012 versus $930 million in the first quarter of 2011, driven primarily by an increase in the average net sales price and, to a lesser extent, an increase in Neulasta unit demand. Combined Neulasta and NEUPOGEN international sales decreased 4 percent to $291 million in the first quarter of 2012 versus $302 million in the first quarter of 2011, due primarily to a decrease in the average net sales price. A mid single-digit percentage point increase in Neulasta unit demand was offset by a decline in NEUPOGEN units due primarily to biosimilar competition.
Enbrel® (etanercept) sales increased 7 percent to $938 million in the first quarter of 2012 versus $875 million in the first quarter 2011, driven primarily by an increase in the average net sales price. ENBREL remains the segment share leader in both the rheumatology and dermatology segments.
Aranesp® (darbepoetin alfa) sales decreased 11 percent to $518 million in the first quarter of 2012 versus $580 million in the first quarter of 2011. U.S. Aranesp sales decreased 19 percent to $202 million in the first quarter of 2012 versus $250 million in the first quarter of 2011, due primarily to a decline in unit demand, offset partially by a mid single-digit percentage point increase in the average net sales price. The unit decline reflects segment contraction resulting from changes to the product label and reimbursement environment that occurred during 2011. International Aranesp sales decreased 4 percent to $316 million in the first quarter of 2012 versus $330 million in the first quarter of 2011, due primarily to a decrease in the average net sales price.
EPOGEN® (epoetin alfa) sales decreased 17 percent to $446 million in the first quarter of 2012 versus $535 million in the first quarter of 2011, reflecting the impact of changes to the label and reimbursement. The decline was comprised of an approximately 30 percent decrease in unit demand driven by a reduction in dose utilization, offset partially by reductions in customer discounts as part of new provider contracts that became effective Jan. 1, 2012.
On a sequential basis, EPOGEN sales decreased 8 percent, comprised of an approximately 20 percent decrease in unit demand driven by the timing of end-user purchases at the end of 2011 and a reduction in dose utilization. These decreases were offset partially by reductions in customer discounts as part of new provider contracts.
Sales of our other, growth-phase products increased 22 percent to $399 million in the first quarter 2012 versus $327 million in the first quarter of 2011. Sales of Sensipar®/Mimpara® (cinacalcet) increased 17 percent to $219 million in the first quarter of 2012 versus $187 million in the first quarter of 2011. Sales of Vectibix® (panitumumab) increased 20 percent to $90 million in the first quarter of 2012 versus $75 million in the first quarter of 2011. Sales of Nplate® (romiplostim) increased 38 percent to $90 million in the first quarter of 2012 versus $65 million in the first quarter of 2011. These increases were driven primarily by global unit growth.
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