B-Cell Lymphoma Protected by SPAK Silencing A group led by Dr. Michael Teitell at UCLA has demonstrated that misregulation of the protein SPAK may contribute to B-cell lymphoma development. Their report can be found in the October 2009 issue of the American Journal of Pathology. B-cell lymphomas are the most frequent human immune system cancers.

Cancer Research Uk Scientists have discovered a completely new route by which leukaemia develops, according to research published in Nature. Scientists from the

Allos Therapeutics, Inc. (Nasdaq:ALTH) announced that last night the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYNTM (pralatrexate injection) for use as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). FOLOTYN is the first and only drug approved by the FDA for this indication and represents a new treatment option for patients with relapsed or refractory PTCL.

IntroductionExpression of the ‘A’ and ‘B’ forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional ‘A’ form of PR as transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics.
Methods:
We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of LAP and TGFbeta1 between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography.
Results:
The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E+P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/ER-alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGFbeta1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild type mice, but is achieved only by treatment with P in PR-A mice.
Conclusions:
These data establish a link between hormonal response, proliferation, modulation of MMP activity and maintenance of basement membrane integrity that depend on a balance in the expression levels of PR-A and B isoforms. Notably, concomitant increased proliferation, due to inhibition of TGFbeta1 activation, and loss of basement membrane integrity, via increased MMP-2 activity, appear to be prerequisites for the PR-A hyperplastic phenotype.

Three MAPK (Mitogen Activated Protein Kinase) intracellular signalling cascades, the ERK (Extra-cellular-Regulated-Kinase) pathway, the p38 pathway and the JNK (c-Jun N-terminal Kinase) pathway function in mammalian cells. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK pathway, in particular, has been implicated as being important. We review the influence of ERK activity on organised association of mammary epithelial cells in 3-D, and in models of breast cancer cell invasion. We assess the importance of EGFR family signalling through ERK in models of breast cancer progression and the influence of ERK on its substrate, the estrogen receptor (ER), in this context. In parallel, we consider the importance of these ERK-centred signalling cascades during the cycle of mammary gland development. Although less well studied, we highlight the instances of signalling through the p38 and JNK pathways with breast cancer progression and mammary gland development.

BERLIN – The potent oral multiple kinase inhibitor sorafenib (NexavarR) combined with the chemotherapy drug capecitabine (XelodaR) significantly improves progression-free survival (PFS) over capecitabine alone in patients with locally advanced or metastatic HER-2 negative breast cancer, according to phase 2b results released at the joint 15th European Cancer Organization (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress.

Researchers from Boston University School of Medicine (BUSM) are recommending that menopausal women on hormone therapy (HT) continue their treatment prior to having their annual mammogram screenings. These recommendations appear as an editorial in the current on-line issue of Journal of the North American Menopause Society.

A new study of New York State data finds that the number of women opting for surgery to remove the healthy breast after a cancer diagnosis in one breast is rising, despite a lack of evidence that the surgery can improve survival. The study also finds that despite extensive press coverage of women who choose to have both breasts removed because of a strong family history of cancer, the rate of this surgery is relatively low and has changed little in the last decade.

Aromatase inhibitors, the same drugs that have buoyed long-term survival rates among breast cancer patients, also carry side effects including joint pain so severe that many patients discontinue these lifesaving medicines. New University of Pennsylvania School of Medicine research, however, has uncovered patterns that may help clinicians identify and help women at risk of these symptoms sooner in order to increase their chances of sticking with their treatment regimen.

Aromatase inhibitors, the same drugs that have buoyed long-term survival rates among breast cancer patients, also carry side effects including joint pain so severe that many patients discontinue these lifesaving medicines. New University of Pennsylvania School of Medicine research, however, has uncovered patterns that may help clinicians identify and help women at risk of these symptoms sooner in order to increase their chances of sticking with their treatment regimen.