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Detroit, MI, United States

The Barbara Ann Karmanos Cancer Institute is located in Detroit, Michigan. It is one of 41 National Cancer Institute-designated comprehensive cancer centers in the United States. The institute has 1,200 staff members, including 300 doctors. Staff treat approximately 12,000 patients each year and operates with a budget of $260 million. It conducts 700 cancer-specific scientific investigations programs and clinical trials each year.Karmanos Cancer Institute became Michigan's first and only hospital focused on cancer on Dec. 1, 2005.The institute has a Phase 1 program, one of only 14 National Cancer Institute -funded Phase 1 programs in the United States. Karmanos is affiliated with Wayne State University School of Medicine and its doctors are faculty members at the medical school. Wikipedia.

Mujtaba T.,Barbara Ann Karmanos Cancer Institute
Discovery medicine | Year: 2011

The ubiquitin-proteasome pathway regulates many basic cellular processes and has been proven to be a promising target for cancer therapy. Bortezomib is the first U.S. Food and Drug Administration (FDA) approved proteasome inhibitor used in the treatment of newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, and mantle cell lymphoma. The anti-cancer mechanisms of bortezomib elucidated by preclinical studies include: upregulation of proapoptotic proteins (e.g., Noxa, IκB), inhibition of NFκB and its anti-apoptotic target genes, suppression of several anti-apoptotic proteins (e.g., Bcl-XL, Bcl-2, and STAT-3), down-regulation of expression of several proteins involved in DNA repair pathways, and induction of endoplasmic reticulum (ER) stress and pro-apoptotic Unfolded Protein Response (UPR). Bortezomib has potent chemo-/radio-sensitizing effects and can overcome traditional drug resistance in tumors when used in combination with potential chemotherapies. Although bortezomib has been successful in improving clinical outcomes when used in hematological malignancies, relapse may occur in those patients who responded initially. Furthermore, some cytotoxicities (such as peripheral neuropathy) were found to be associated with bortezomib treatment. These observations have encouraged researchers to search for the next generation proteasome inhibitors (including carfilzomib and marizomib) that could overcome bortezomib resistance and have improved properties, reduced toxicities, and broader anticancer activities, based on the lessons learned from the mechanisms and use of bortezomib. This review summarizes the current status of bortezomib as well as several other proteasome inhibitors that are currently under clinical and preclinical investigation. © Discovery Medicine Source

Kanwar J.,Barbara Ann Karmanos Cancer Institute
Frontiers in bioscience (Elite edition) | Year: 2012

Over the past decade many scientific and medical studies have focused on green tea for its long-purported health benefits. There is convincing evidence that tea is a cup of life. It has multiple preventive and therapeutic effects. This review thus focuses on the recent advances of tea polyphenols and their applications in the prevention and treatment of human cancers. Of the various polyphenols in tea, (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant, and active compound studied in tea research. EGCG inhibits several molecular targets to inhibit cancer initiation and modulates several essential survival pathways to block cancer progression. Herein, we describe the various mechanisms of action of EGCG and also discuss previous and current ongoing clinical trials of EGCG and green tea polyphenols in different cancer types. Source

Ferrara F.,Stem Cell Transplantation Unit | Schiffer C.A.,Barbara Ann Karmanos Cancer Institute
The Lancet | Year: 2013

The outlook for patients with acute myeloid leukaemia has improved in the past 30 years. Unlike other cancers, much of this progress is attributable to refinement of supportive treatment, rather than the introduction of new drugs. New antibacterial and antifungal agents, antiemetics, and improved transfusion support have decreased the rate of early death, and morbidity and mortality from allogeneic stem cell transplantation has been substantially reduced. However, more than half of young adult patients and about 90% of older patients still die from their disease. Refractoriness to initial induction treatment and, more frequently, relapse after complete remission, are still the main obstacles to cure. Accordingly, new treatment approaches with mechanisms of action different from those of conventional chemotherapy are needed. Our knowledge of the various chromosomal and molecular abnormalities implicated in the pathogenesis of the many subtypes of the disease has greatly expanded; as a result, clinical research is moving towards the investigation of new non-cytotoxic agents in combination with chemotherapy. The goal is to target the molecular abnormalities identified at diagnosis; however, several aberrations can coexist in subclones of acute myeloid leukaemia, making the disease less likely to be inhibited by a single agent. © 2013 Elsevier Ltd. Source

Bepler G.,Barbara Ann Karmanos Cancer Institute
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non-small-cell lung cancer (NSCLC). Eligible patients were randomly assigned 2:1 to the trial's experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if both were high. In the control arm, patients received gemcitabine/carboplatin. The trial was powered for a 32% improvement in 6-month progression-free survival (PFS). Of 331 patients registered, 275 were eligible. The median number of cycles given was four in both arms. A tumor rebiopsy specifically for expression analysis was required in 17% of patients. The median time from informed consent to expression analysis was 11 days. We found no statistically significant differences between the experimental arm and the control arm in PFS (6.1 months v 6.9 months) or overall survival (11.0 months v 11.3 months). A subset analysis revealed that patients with low levels for both proteins who received the same treatment in both treatment arms had a statistically better PFS (P = .02) in the control arm (8.1 months) compared with the experimental arm (5.0 months). This demonstrates that protein expression analysis for therapeutic decision making is feasible in newly diagnosed patients with advanced-stage NSCLC. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% (47 of 53) of patients. Source

This protocol requires 2-4 h and presents a method for injecting tumor cells, cancer stem cells or dispersed biopsy material into subcutaneous or orthotopic locations within recipient mice. The tumor cells or biopsy are mixed with basement membrane matrix proteins (CultrexBME or Matrigel) at 4 °C and then injected into recipient animals at preferred anatomical sites. Tumor cells can also be co-injected with additional cell types, such as fibroblasts, stromal cells, endothelial cells and so on. Details are given on appropriate cell numbers, handling and concentration of the basement membrane proteins, recipient animals, injection location and techniques. This procedure enables the growth of tumors from cells or biopsy material (tumor graft) with greater efficiency of take and growth, and with retention of the primary tumor phenotype based on histology. Co-injection with additional cell types provides more physiological models of human cancers for use in drug screening and studying cancer biology. Source

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