Don't die from Cancer

Therapeutic antibodies for the treatment of pancreatic cancer.

noreply@blogger.com (Unknown) — Mon, 20 Sep 2010 20:42:00 +0000

Abstract
Pancreatic cancer is a devastating disease with the worst mortality rate and an overall 5-year survival rate lower than 5%. In the U.S., this disease is the fourth leading cause of death and represents 6% of all cancer-related deaths. Gemcitabine, the current standard first-line treatment, offers marginal benefits to patients in terms of symptom control and prolongation of life. Since 1996, about 20 randomized phase III trials have been performed to improve the efficacy of gemcitabine, with little success regarding a significant improvement in survival outcomes. The need for novel therapeutic strategies, such as target therapy, is obvious. Monoclonal antibodies have finally come of age as therapeutics and several molecules are now approved for cancer therapies. This review aims to give a general view on the clinical results obtained so far by antibodies for the treatment of pancreatic cancer and describes the most promising avenues toward a significant improvement in the treatment of this frustrating disease

Chames P, Kerfelec B, Baty D.

INSERM U624, GDR2352, Marseille Cedex, France

Mastitis and the risk of breast cancer.

noreply@blogger.com (Unknown) — Wed, 19 Aug 2009 19:45:00 +0000

BACKGROUND: Many cancers arise from sites of infection and inflammation. Results from animal studies indicate that inflammatory cells may facilitate neoplastic processes by orchestrating the tumor microenvironment. Little is known about the role of inflammation in the etiology of breast cancer. The aim of this study was to examine possible associations between a history of mastitis requiring hospitalization and subsequent risk of breast cancer.

METHODS: This cohort study of 2,577,565 women used data from several Swedish population-based registers, including the Inpatient Register and the Cancer Register. The risk of breast cancer was assessed by Poisson regression modeling.

RESULTS: We identified 8411 women in the Inpatient Register with a discharge diagnosis of mastitis. Of these, 106 had a subsequent diagnosis of breast cancer recorded in the Cancer Register. Compared with women who had no recorded mastitis, the incidence rate of breast cancer (regardless of laterality) was higher in women with mastitis, with an incidence rate ratio of 1.23 (95% confidence interval [CI] = 1.02-1.49) following adjustment for age, calendar time, age at first birth and parity. In the group of women among whom information on laterality was available for both the mastitis and the malignancy (n = 87), side of lesions corresponded for 52% (95% CI = 41%-62%), which is what could be expected by chance.

CONCLUSIONS: The overall risk of breast cancer was slightly elevated in women with a history of mastitis recorded in the Inpatient Register. The absence of a correlation between laterality of lesions, however, does not support a causal association between inflammation and the development of breast cancer.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.Lambe M, Johansson AL, Altman D, Eloranta S.

Cancer Stem Cells in Pediatric Brain Tumors.

noreply@blogger.com (Unknown) — Sun, 14 Jun 2009 15:12:00 +0000

Central nervous system (CNS) tumors remain the leading cause of death among pediatric neoplasms. Although standard therapies cure many pediatric CNS tumors, the long-term cognitive and physical consequences of these therapies are devastating. Furthermore, recurrent disease carries a dismal prognosis. Although recent studies have focused on molecular mechanisms that underlie the initiation and progression of adult glioblastoma multiforme (GBM), these tumors differ phenotypically and at a molecular level from pediatric brain tumors. Recent investigations have identified a stem cell population, termed "brain tumor stem cells" (BTSC) within the heterogeneous cell populations that comprise malignant brain tumors which may be partly responsible for the resistance to current therapies. These have been identified in several pediatric tumors including medulloblastoma, ependymomas, and malignant gliomas. By exploiting molecular differences present within these heterogeneous populations of brain tumor cells, we may be able to achieve specific eradication of BTSC and long-lasting remissions, while causing less toxicity to normal tissues. In this review, we describe the issues surrounding the identification and characterization of BTSC, the molecular biology of BTSC for different pediatric brain tumors, and suggest future avenues for the development of treatments for this devastating disease.

Lasky JL 3rd, Choe M, Nakano I.
Department of Neurosurgery, David Geffen School of Medicine at UCLA, USA. INakano@mednet.ucla.edu

Increased CA 19-9 level in patients without malignant disease.

noreply@blogger.com (Unknown) — Thu, 21 May 2009 21:55:00 +0000

Abstract Background: The measurement of carbohydrate antigen 19-9 (CA 19-9) is recommended for the diagnosis and follow-up of pancreatic cancer. However, increased CA 19-9 has also been reported in patients with various benign diseases of the lung. We aimed to elucidate the pulmonary radiographic abnormalities and laboratory results associated with increased concentrations of CA 19-9. Methods: This study was performed using a case-controlled design. Cases included all participants in a cancer screening program who had an increased CA 19-9 concentration (>37 U/mL), but without a diagnosis of malignancy. Age- and sex-matched participants with normal CA 19-9 levels were enrolled as controls. Laboratory results and radiographic features were compared. Results: In total, 119 participants with increased CA 19-9 concentrations and 476 controls were included. A higher erythrocyte sedimentation rate (ESR) [adjusted odd ratio (aOR), 1.03; 95% confidence interval (CI), 1.01-1.05], higher hemoglobin A(1c) (HbA(1c)) (aOR, 1.28; 95% CI, 1.05-1.56), bronchiectasis (aOR, 2.48; 95% CI, 1.22-5.02), bronchiolitis (aOR, 3.93; 95% CI, 1.88-8.22), emphysema (aOR, 2.67; 95% CI, 1.32-5.40), and interstitial fibrosis (aOR, 10.62; 95% CI, 2.03-55.44) were independent factors for increased CA 19-9. Conclusions: CA 19-9 concentrations, as well as increased ESR and HbA(1c), can be increased in patients with various lung abnormalities. Clin Chem Lab Med 2009;47.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

Preoperative Ca-125 level predict optimal cytoreduction in patients with advanced ovarian carcinoma?

noreply@blogger.com (Unknown) — Sun, 04 Jan 2009 00:42:00 +0000

Abstract
BACKGROUND: Preoperative Ca-125 level has been used as a predictor of optimal cytoreduction in advanced ovarian carcinoma . Yet, controversy exists regarding the ability of the tumor marker to predict optimal debulking and moreover of the proper cut-off limit to do so.

METHODS: The preoperative Ca-125 levels of 426 patients with Stage III/IV ovarian carcinoma from a single institution were correlated with surgical outcome. Optimal was considered the cytoreduction if the largest residual tumor was < or equal to 1 cm in diameter. Receiver operation characteristic (ROC) curve data were combined with interval likelihood ratios at various Ca-125levels to determine the cut-off level with the maximum prognostic power. Sensitivity, specificity, positive and negative predictive values and accuracy were also calculated.

RESULTS: Preoperative Ca-125 proved to be a reliable predictor for optimal cytoreduction. The area under curve of the ROC curve was 0.89, 98% C.I.=[0.828-0.952], indicating very good discriminating capability. The level of 500 IU/ml was found to have the most predictive power. The sensitivity of Ca-125 at that level was 78.5%, the specificity 89.6%, the positive predictive value 84.2%, the negative predictive value 85.4% and its accuracy 85%. Furthermore, the likelihood ratio for correct discrimination between optimal and sub-optimal cytoreduction, dropped sharply from 6.33, 95% C.I. [5.19-10.91] at the level of 500 IU/ml to 0.58, 95% C.I. [0.21-1.63] at the level of 600 IU/ml.

CONCLUSIONS: Our data indicate that preoperative Ca-125 is a good predictor for optimal cytoreduction. the best threshold for this prediction proved to be 500 IU/ml. These patients may be candidates for neo-adjuvant chemotherapy treatment. Nevertheless, all clinical and radiological findings must be co-evaluated

Vorgias G, Iavazzo C, Savvopoulos P, Myriokefalitaki E, Katsoulis M, Kalinoglou N, Akrivos T.
Department of Gynecology, Metaxa Memorial Cancer Hospital, Piraeus, Greece

The Basis of Racial Differences in the Incidence of Thyroid Cancer

noreply@blogger.com (Unknown) — Tue, 05 Feb 2008 18:41:00 +0000

BACKGROUND: The incidence of thyroid cancer in black Americans is half that in white Americans. It is unknown whether this gap represents a population difference in disease or is attributable to inferior cancer screening in the black population.

METHODS: A population-based cohort study of 53,990 patients (1973-2003) was performed using the National Cancer Institute's Surveillance Epidemiology End Results database. Socioeconomic variables were explored using the Healthcare Cost and Utilization Project database and macroeconomic data.

RESULTS: Since 1973, thyroid cancer incidence among whites has increased 150.2% (4.0 to 9.9 of 100,000), while incidence among blacks has increased 73.2% (3.0 to 5.1 of 100,000). Across 17 regions, the incidence correlated with the percentage of the population with health insurance (r = 0.56, P = .02). Regression analysis suggested that half of the black-white incidence gap might be attributable to differences in health insurance status. Patients with thyroid cancer were more likely to be insured or reside in wealthier ZIP codes. Black patients were more likely to present at advanced age (RR 1.08, P < .0001) and with tumors >4 cm in size (RR 1.13, P <.0001). Black patients were slightly less likely to present with advanced disease (RR 0.96, P = .0008). Cancer-specific mortality was identical in the two populations.

DISCUSSION: Sociodemographic data and differences at presentation support a small detection disparity in thyroid cancer, which may contribute to part of the incidence gap. However, this effect is not sufficiently strong to fully explain the incidence gap. A population difference in the incidence of disease may be coexistent.

Head & Neck Service, Department of Otolaryngology, New York University Cancer Institute, New York University School of Medicine, New York, NY, USA, Ann Surg Oncol. 2008 Feb 2

NTU discovery may help cardiovascular, cancer experiments

noreply@blogger.com (Unknown) — Wed, 30 Jan 2008 18:39:00 +0000

A research team at National Taiwan University (NTU) has discovered a gene that curbs liver cancer metastasis and another that triggers coronary artery disease, the team's instructor said yesterday.

Lin Shu-hua (林淑華), a professor at the university's Department of Clinical Laboratory Sciences and Medical Biotechnology, said her research team's discovery came from experiments with the "knockout mouse" technique, which uses a mouse that has had the function of one or more of its genes deleted or made non-functional, to study the correlations of genes and diseases.

LIVER CANCER

Lin said the team's discovery would help in developing new medicine and designing clinical experiments for liver cancer and cardiovascular disease.

She said that the X gene -- one of the two genes isolated -- helps curb liver cancer metastasis. Her team implanted liver cancer cells in mice, knocked out their X genes and observed metastasis and tumor clusters on them in the experiment.

The discovery might be helpful in improving the effects of liver cancer treatment if the correlation between the disease and the gene, which Lin described as "a guard" protecting the liver, is established through further experiments, she said.

In addition, the team found that the thromboxane A2 gene, or TXA2, causes coronary artery narrowing. The team's experiment knocked out that gene from mice, fed them high cholesterol food and found the percentage of coronary artery narrowing declined.

The team performed cardiac catheterization operations on the same mice and found that blood vessel damage was rare after the operations.

Lin said patients who receive cardiovascular stent operations usually have a 50 percent risk of suffering coronary artery narrowing following the operation.

LOWER CHANCES

The discovery assumes that medicine that curbs the TXA3 gene would lower the chances of getting cardiovascular disease, Lin said.

The knockout mouse technique has the greatest potential in the field.

Three scientists were awarded the Nobel Prize for Medicine last year for producing the first knockout mice. Oliver Smithies, one of the scientists, was Lin's instructor.

MIT IDs link between brain tumor proteins

noreply@blogger.com (Unknown) — Wed, 12 Dec 2007 19:19:00 +0000

CAMBRIDGE, Mass. -- MIT researchers have identified a critical link between two proteins found in brain tumors , a discovery that could eventually help treat a form of brain cancer that kills 99 percent of patients.

Glioblastoma multiforme (GBM), the most aggressive brain tumor in adults, strikes about 15,000 people in the United States each year. GBM is currently treated with a combination of surgery, radiation and chemotherapy, but those treatments have proven ineffective. Most patients die within a year.

Now, MIT scientists have uncovered a connection between two proteins found in the tumor cells , and they have demonstrated that attacking both of those proteins kills tumor cells much more effectively than targeting either one alone.

The team focused on a protein called EGFRvIII , a mutated form of the cell receptor for epidermal growth factor (EGF). The mutated receptor, which is found in approximately a quarter of GBM tumors, is continuously active and relentlessly pushes cells to keep growing and dividing.

Doctors have tried treating GBM patients with drugs that inhibit EGFRvIII, but they have had little effect. This could be because the continuous stimulation of the receptor is so intense and because the receptor interacts with numerous other proteins that also promote tumor growth, said White, who is also affiliated with MIT’s Center for Cancer Research and its Computational and Systems Biology Initiative.

Serum Tumor Markers May Predict Overall and Disease Specific Survival in Patients With Clinically Organ Confined Invasive Bladder Cancer

noreply@blogger.com (Unknown) — Fri, 23 Nov 2007 19:08:00 +0000

Purpose
We assessed the value of increased levels of carcinoembryonic antigen , CA (cancer antigen) 125 and CA (carbohydrate antigen) 19-9 in predicting the survival of patients with clinically organ confined bladder cancer .

Materials and Methods
Serum levels of carcinoembryonic antigen , CA 125 and CA 19-9 were measured prospectively in all patients scheduled for cystectomy for clinically organ confined bladder cancer between September 1999 and May 2004. The association between marker levels and overall and disease specific survival rates was assessed, and multivariate analysis was performed to determine the predictive value for outcome.

Results
The study included 91 patients with a median followup of 33.5 months (range 3 to 85). Overall and disease specific 5-year survival rates were 47% and 66%, respectively. On univariate analysis CA 19-9 and CA 125 were found to be statistically significant predictors (p <0.001) of overall survival. Respective 1, 2 and 5-year rates were CA 19-9 increased in 65%, 35% and 14%, normal in 83%, 70% and 53%, and CA 125 increased in 50%, 33% and 8%, and normal in 85%, 70% and 55%. CA 19-9 was also a statistically significant predictor (p <0.001) of disease specific survival, with 1, 2 and 5-year rates of 70%, 35% and 24% in patients with high levels vs 89%, 86% and 73% in patients with normal levels. On multivariate Cox regression analysis CA 19-9 (OR 1.5, 95% CI 1.1–2.3, p = 0.02) was an independent predictor of disease specific survival.

Conclusions
Increased CA 19-9 and/or CA 125 levels before cystectomy in patients with clinically organ confined muscle invasive bladder cancer are associated with poor outcome. CA 19-9 appears to be an independent predictor of disease specific mortality. Further larger scale studies are needed to confirm these results.

doi:10.1016/j.juro.2007.08.017
aInstitute of Urology, Rabin Medical Center, Beilinson Campus, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel

Proteomic Approaches to Tumor Marker Discovery

noreply@blogger.com (Unknown) — Fri, 19 Oct 2007 15:25:00 +0000

Identification of Biomarkers for Ovarian Cancer. Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids . Conclusions.—The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125 . Additional studies are required to further validate these biomarkers. Source: Archives of Pathology and Laboratory Medicine: Vol. 126, No. 12, pp. 1518–1526.

What Are Tumor Markers

noreply@blogger.com (Unknown) — Mon, 15 Oct 2007 04:12:00 +0000

American Cancer Society says that tumor markers are substances that can be found in the body (usually in the blood or urine) when cancer is present. Tumor Markers can be products of the cancer cells themselves or of the body in response to cancer or other conditions. Most tumor markers are proteins .

According to Medicinenet.com the most widely used biochemical blood test for liver cancer - hepatocellular carcinoma (HCC) is alpha-fetoprotein (AFP) , which is a protein normally made by the immature liver cells in the fetus. At birth, infants have relatively high levels of alpha-fetoprotein (AFP) , which fall to normal adult levels by the first year of life.

Did you know that the first modern tumor marker used to detect cancer was human chorionic gonadotropin (HCG), the substance doctors look for in pregnancy tests. Women whose pregnancy has ended but whose uterus continues to be enlarged are tested for the presence of human chorionic gonadotropin (HCG).

According to published reports, The first success in developing a blood test for a common cancer was in 1965, when carcinoembryonic antigen (CEA) was found in the blood of some patients with colon cancer. By the end of the 1970s several other blood tests had been developed for different cancers. The new markers were often given numeric labels. There was Cancer Antigen CA 19-9 for colorectal and pancreatic cancer, CA 15-3 for breast cancer, and CA 125 for ovarian cancer.

The only tumor marker that currently allows doctors to detect early disease and is used in screening is the prostate-specific antigen (PSA) test. PSA was discovered around the same time as the others, but it’s been in widespread use for screening since the early 1990s because it has some advantages over them.

Alpha-fetoprotein (AFP): AFP is most useful in following the response to treatment for liver cancer (hepatocellular carcinoma).

Beta-2-microglobulin (B2M): B2M blood levels are elevated in multiple myeloma, chronic lymphocytic leukemia (CLL), and some lymphomas. Levels may also be elevated in some non-cancerous conditions, such as kidney disease

Carcinoembryonic antigen (CEA): CEA is the preferred tumor marker for following patients with colorectal cancer during or after treatment, although it is not useful as a screening or diagnostic test

Immunoglobulins: Immunoglobulins are antibodies, which are blood proteins normally made by immune system cells to help fight germs. There are several types of immunoglobulins, including IgA, IgG , IgD, and IgM . Bone marrow cancers such as multiple myeloma and Waldenstrom macroglobulinemia often result in too many immunoglobulins in the blood (as well as in the urine)

Neuron-specific enolase (NSE): NSE, like chromogranin A, is a marker for neuroendocrine tumors such as small cell lung cancer, neuroblastoma, and carcinoid tumors. It is not used as a screening test. It is most useful in the follow-up of patients with small cell lung cancer or neuroblastoma.

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