Targeting mTOR in HIV-Negative Classic Kaposi's Sarcoma

A 66-year old female with HIV-negative classic Kaposi's sarcoma responded to mTOR targeting by rapamycin. The response was well documented by PET-CT. This case provides supporting evidence that the mTOR pathway may be important in the tumorigenesis of KS and that rapamycin may have activity in this disease

Gemcitabine in Bone Sarcoma Resistant to Doxorubicin-Based Chemotherapy

Subjects and Methods: Seven patients with progressive localized or metastatic chemo-resistant osteosarcoma were treated by gemcitabine.The protocol included gemcitabine 1000 mg/m2/w for 7 consecutive weeks, followed by 1 week rest. If no progression was observed,maintenance by gemcitabine 1000 mg/m2/w for 3 weeks every 28 days was given until failure was clinically or radiologically evident

Periosteal Ewing's Sarcoma: Report of Two New Cases and Review of the Literature

Background. The origin of Ewing's sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better prognosis when confined between periosteum and bone. Is it the same for periosteal Ewing's sarcoma

Radiation Therapy for Palliation of Sarcoma Metastases: A Unique and Uniform Hypofractionation Experience

Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma

Application of a Static Fluorescence-based Cytometer (the CellScan) in Basic Cytometric Studies, Clinical Pharmacology, Oncology and Clinical Immunology

The CellScan apparatus is a laser scanning cytometer enabling repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. The CellScan may serve as a tool for diagnosis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) as well as other autoimmune diseases by monitoring FP changes in peripheral blood lymphocytes (PBLs) following exposure to autoantigenic stimuli. Changes in FI and FP in atherosclerotic patients' PBLs following exposure to various stimuli have established the role of the immune system in atherosclerotic disease. The CellScan has been evaluated as a diagnostic tool for drug-allergy, based on FP reduction in PBLs following incubation with allergenic drugs. FI and FP changes in cancer cells have been found to be well correlated with the cytotoxic effect of anti-neoplastic drugs. In conclusion, the CellScan has a variety of applications in cell biology, immunology, cancer research and clinical pharmacology

High Frequency of Skin-homing Melanocyte-specific Cytotoxic T Lymphocytes in Autoimmune Vitiligo

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. Using tetrameric complexes of human histocompatibility leukocyte antigen (HLA) class I to identify antigen-specific T cells ex vivo, we observed high frequencies of circulating MelanA-specific, A*0201-restricted cytotoxic T lymphocytes (A2–MelanA tetramer+ CTLs) in seven of nine HLA-A*0201–positive individuals with vitiligo. Isolated A2–MelanA tetramer+ CTLs were able to lyse A*0201-matched melanoma cells in vitro and their frequency ex vivo correlated with extent of disease. In contrast, no A2–MelanA tetramer+ CTL could be identified ex vivo in all four A*0201-negative vitiligo patients or five of six A*0201-positive asymptomatic controls. Finally, we observed that the A2–MelanA tetramer+ CTLs isolated from vitiligo patients expressed high levels of the skin homing receptor, cutaneous lymphocyte-associated antigen, which was absent from the CTLs seen in the single A*0201-positive normal control. These data are consistent with a role of skin-homing autoreactive melanocyte-specific CTLs in causing the destruction of melanocytes seen in autoimmune vitiligo. Lack of homing receptors on the surface of autoreactive CTLs could be a mechanism to control peripheral tolerance in vivo

Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C

Treatment of chronic hepatitis C with pegylated interferon (peginterferon) and ribavirin can cause or exacerbate depression but its effects on cognitive function are largely unknown. The aim of this study was to determine whether treatment with peginterferon and ribavirin adversely impacts cognitive function in patients with chronic hepatitis C. Prior nonresponders to interferon were retreated with peginterferon alfa-2a and ribavirin for 24 (n = 177) or 48 weeks (n = 57) in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial. Cognitive function was prospectively assessed using a battery of 10 standardized neuropsychological tests at weeks 0, 24, 48, and 72. Cognitive impairment was defined based upon a global deficit score. The Beck Depression Inventory and Brief Symptom Inventory were used to assess mood status. The 57 subjects who completed 48 weeks of antiviral therapy reported significant increases in difficulty concentrating, emotional distress, and symptoms of depression, all of which improved after cessation of therapy [ P < 0.0001, analysis of variance (ANOVA)]. Nonetheless, the frequency of cognitive impairment did not increase during the first 24 weeks of treatment in 177 patients (34% versus 32%, P = 0.64) nor in the 57 patients completing 48 weeks of treatment ( P = 0.48, ANOVA). Conclusion: Retreatment of prior non-responders with peginterferon and ribavirin was not associated with objective evidence of cognitive impairment as measured by a comprehensive battery of neuropsychological tests. The lack of cognitive impairment is reassuring and suggests that self-reported symptoms of cognitive dysfunction are more likely related to the systemic and psychiatric side effects of antiviral treatment rather than measurable changes in cognition. (H EPATOLOGY 2007;45:1154–1163.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56062/1/21633_ftp.pd

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel