Therapeutic antibodies for the treatment of pancreatic cancer.

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.

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.

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.


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

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?

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

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

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.


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.


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.