Wajeeha Razaq

Primary Central Nervous System Mucosa-Associated Lymphoid Tissue Lymphoma: Case Report and Literature Review

Primary presentation of intradural non-Hodgkin lymphoma is rare. Recently, B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) have been recognized as an important pathologic subtype. When MALT lymphomas present in the central nervous system (CNS), they are distinguishable from primary high-grade CNS lymphomas. We present the clinicopathologic features of 5 patients with primary CNS MALT lymphoma treated at our institution from 1999 to 2006. Four out of 5 patients were women, and all patients presented with headaches, focal motor deficits, or cranial nerve palsy. Radiologic studies demonstrated ill-defined dural masses in 3 and well-defined masses in 2 patients. Pathology revealed small to medium-sized cells with a moderate amount of cytoplasm and irregular nuclear borders, expressing pan B-cell markers (CD19, CD20, and CD79a) but lacking CD10, CD23, and cyclin D1, confirming low-grade MALT lymphoma. Plasma cells were encountered in all the biopsies with variable reactive T-cell infiltration. wedge chain restriction was seen in 3 patients. Therapy consisted of either surgical resection, whole-brain radiation, or systemic or intrathecal chemotherapy. There was no evidence of recurrence or systemic relapse in 4 patients at 4 years of follow-up. One patient died in 2 months, unrelated to CNS lymphoma. This case series illustrates the rare occurrence of low-grade dural B-cell lymphoma and the need to consider this entity in the differential diagnosis of CNS lesions.

E-selectin Targeting PEGylated-thioaptamer Prevents Breast Cancer Metastases

E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for the prevention of hematogenous metastasis through the blockade of CD44high breast cancer cells (BCa) adhesion to E-selectin-expressing premetastatic endothelial niche. The current study focuses on developing a PEGylated E-selectin targeting thioaptamer with improved pharmaceutical properties. A serial deletion of stem-loops reveled that loop-1 and -2 (ESTA7) are the minimally effective backbone structure necessary to obtain inhibition of the E-selectin/CD44 interaction and shear resistant adhesion of CD44high BCa to E-selectin-expressing human endothelial cells (HMVECs) at a level equal to ESTA. Chemical conjugation of methoxy-polyethylene-glycol (PEG) at the sizes of 5 and 10 kDa did not interfere with ESTA7-mediated shear-resistant adhesion. However, in vivo study demonstrated that only 10 kDa PEG-conjugated ESTA7 (ESTA7-p10) retains the activity to inhibit metastases at a level equal to parental ESTA. Additionally, a single intravenous injection of ESTA7-p10 inhibited the development of lung, brain, and bone metastases of MDA-MB-231, through the blockade of E-selectin. Moreover, PEGylation led to an extension of elimination half-life and increase of AUC, resulting in superior inhibition of metastasis development compared to parental ESTA with a longer interval between dosing in a spontaneous metastasis model. Lastly, repeated intravenous administration of ESTA7-p10 was tolerated in mice, highlighting the potential prophylactic application of ESTA7-p10 for metastasis prevention.E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for the prevention of hematogenous metastasis through the blockade of CD44high breast cancer cells (BCa) adhesion to E-selectin-expressing premetastatic endothelial niche. The current study focuses on developing a PEGylated E-selectin targeting thioaptamer with improved pharmaceutical properties. A serial deletion of stem-loops reveled that loop-1 and -2 (ESTA7) are the minimally effective backbone structure necessary to obtain inhibition of the E-selectin/CD44 interaction and shear resistant adhesion of CD44high BCa to E-selectin-expressing human endothelial cells (HMVECs) at a level equal to ESTA. Chemical conjugation of methoxy-polyethylene-glycol (PEG) at the sizes of 5 and 10 kDa did not interfere with ESTA7-mediated shear-resistant adhesion. However, in vivo study demonstrated that only 10 kDa PEG-conjugated ESTA7 (ESTA7-p10) retains the activity to inhibit metastases at a level equal to parental ESTA. Additionally, a single intravenous injection of ESTA7-p10 inhibited the development of lung, brain, and bone metastases of MDA-MB-231, through the blockade of E-selectin. Moreover, PEGylation led to an extension of elimination half-life and increase of AUC, resulting in superior inhibition of metastasis development compared to parental ESTA with a longer interval between dosing in a spontaneous metastasis model. Lastly, repeated intravenous administration of ESTA7-p10 was tolerated in mice, highlighting the potential prophylactic application of ESTA7-p10 for metastasis prevention.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice.

The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions.

Bone Targeted Therapies for Bone Metastasis in Breast Cancer

Cancer metastasis to the bone develops commonly in patients with various malignancies, and is a major cause of morbidity and diminished quality of life in many affected patients. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to the bone metastasis. The tendency of cancer cells to metastasize to bone is probably the end result of many factors including vascular pathways, the highly vascular nature of the bone marrow (which increases the probability that cancer cells will be deposited in bone marrow capillaries), and molecular characteristics of the cancer cells that allow them to adapt to the bone marrow microenvironment. The goals of treating osseous metastases are manifold. Proper treatment can lead to significant improvements in pain control and function, and maintain skeletal integrity. The treatment plan requires a multidisciplinary approach. Widespread metastatic disease necessitates systemic therapy, while a localized problem is best managed with surgery, external beam radiotherapy, or both. Patients with bone metastasis can have prolonged survival, and proper management can have a significant impact on their quality of life. We will review the factors in this article that are promising molecular bone-targeted therapies or will be likely targets for future therapeutic intervention to restore bone remodeling and suppress tumor growth.

Successful Treatment of Refractory Idiopathic Hypereosinophilic Syndrome With Etoposide

Idiopathic hypereosinophilic syndrome represents a heterogenous group of leukoproliferative disorders with hypereosinophilia of an unknown etiology resulting in multiorgan dysfunction. The disease can involve any organ but commonly involves heart, nervous system, skin, and gastrointestinal system. Steroids and chemotherapy agents remain the mainstay of the treatment to suppress organ damage and eradicate eosinophilia. We are presenting an interesting patient of idiopathic hypereosinophilic syndrome with cardiac involvement who was refractory to many chemotherapeutic drugs including imatinib but had an excellent response to etoposide. Although the mechanism by which etoposide works in this disease is not well understood, it has been tried in the past with success. The patient is off therapy for the past 24 months with stable eosinophil count.

Erratum to: The effect of soluble E-selectin on tumor progression and metastasis

Author details Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, USA. Thomas Jefferson University, Pharmaceutical Sciences, 1020 Locust St, Philadelphia, PA 19107, USA. John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USA. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, USA. Department of Internal Medcine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th, Oklahoma City, OK 73104, USA. Department of Pathology, Medical College of Wisconsin Cancer Center, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, 975 NE 10th, Oklahoma City, OK 73104, USA.

Aromatase Inhibitors and Osteoporosis - Risk, Prevention and TreatmentReview

Breast cancer is the most common cancer diagnosed and second leading cause of death among women in United States. Surgical resection with or without radiation remains the cornerstone of treatment for early stage breast cancer. Systemic adjuvant therapy with Tamoxifen or Aromatase Inhibitors (AIs) is indicated for Estrogen/Progesterone receptor (ER/PR) positive non metastatic breast cancer, depending upon their menopausal status. AIs are the drug of choice in postmenopausal women. They block or prevent estrogens from stimulating the growth of cancer by inhibiting aromatase from converting androgen into estrogen. According to an updated 2004 assessment from the American Society of Clinical Oncology, AIs are recommended to be used in adjuvant therapy initially or after Tamoxifen use for postmenopausal women with ER/PR positive breast cancer.

Circulating Tumor Cells in Breast Cancer: A Potential Liquid Biopsy

Circulating tumor cells (CTCs) have emerged as a new generation of liquid biomarker that allows for noninvasive longitudinal disease monitoring. CTCs represent a rare cell population in the blood, surrounded by billions of hematopoietic cells. Due to the rarity of CTCs in the blood, the isolation of pure CTCs’ populations has proven to be challenging. However, a number of new technologies have emerged using CTCs cytometric/immunological and physical characteristics. Currently, patients with greater than 5 CTCs have a shorter progression-free survival, as compared with those with less than 5 CTCs per 7.5 ml of whole blood. Although the CTC count itself is an independent prognostic marker, the field is shifting toward understanding metastasis-relevant marker expression on CTCs for the improvement of the prognostic significance of CTCs. This chapter first introduces the principles of CTC isolation and detection methods, then the clinical utility of CTCs for prediction of prognosis and therapy response. Lastly, the heterogeneity of CTCs will be discussed.

Concurrent colon adenocarcinoma and hepatoid lung adenocarcinoma with normal serum level and negative immunostain of alpha-fetoprotein

1College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA 2Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA 3Department of Radiation Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA 4Hematology/Oncology Section, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA

Reversible peripartum cardiomyopathy in a patient with prior exposure to interferon

Peripartum cardiomyopathy creates complications for 1 in 3000 to 4000 pregnant women in the US. As this rare condition is associated with a high mortality rate (50% to 85%), it has been investigated to define the possible associated causes. Several factors including hypertension, nutritional and dietary discrepancies, and, recently, myocarditis are being implicated, but the mechanism of cardiac injury is yet to be discovered. Here we present an interesting case of possible interferon-induced reversible peripartum cardiomyopathy. The patient, with a diagnosis of chronic myelogenous leukemia, had been given interferon for 6 years. The therapy was discontinued when she became pregnant, and later she presented with symptoms of heart failure 6 weeks after her c-section. Interferon is an immunomodulating agent and used as an antiviral and an anticancer agent. Interferon-related dilated cardiomyopathy has been described as a rare side effect of the drug, the mechanism of which is unknown. There is compelling data supporting the fact that both peripartum cardiomyopathy and interferon-related cardiomyopathy are autoimmune disorders; so it is suggested that interferon therapy given in the past can have an additive effect in causing dilated cardiomyopathy. It is therefore advisable to follow closely those pregnant patients; who received interferon therapy in the past, for symptoms of cardiac failure, as there can be synergistic action between interferon and pregnancy causing dilated cardiomyopathy.