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Table II. Sensitivities of NM3 and UV40 to genotoxic agents and their correction following transfection of the human FANCG cDNA Fold sensitivity of cell line D37 AA8 D37 mutant or transformant ; Genotoxic agent Mitomycin C DEB Melphalan Chlorambucil Bleomycin Streptonigrin Camptothecin Etoposide EMS MMS D37 AA8 wildtype ; 130 nM 5.1 M 185 nM 29 nM 0.9 mU ml 9.7 nM 41 nM 250 nM 1.5 mM 110 M NM3 NM3-FANCG UV40 UV40-FANCG 4.3 3.0.
Andrew: This is Andrew Schorr with Patient Power and welcome back to another one of our biweekly webcasts on nmh in the HealthNet section, where we connect you with leading Northwestern experts on important health topics. And one of the ones we've been covering lately is lung cancer which, unfortunately, is an all-too-common cancer and all too often is fatal. But we're making progress. So this is really our series now is to help you connect with the latest information and leading Northwestern experts to understand where we are and how you can get the best care for you or someone you love. Just a couple of weeks ago we did a program with Matthew Blum, who is a lung cancer surgical specialist and also leads the multidisciplinary team there. He explained surgical approaches. Today we have as a guest Dr. Jyoti Patel, who is a medical oncologist. She's an assistant professor of Medicine in the Division of Hematology Oncology at the Feinberg School of Medicine at Northwestern University. She's a member of the Robert H. Lurie Comprehensive Cancer Center and is certainly one of the leading thoracic oncologists in the country and is one you can see at Northwestern Memorial Hospital. Dr. Patel, welcome to the program. Dr. Patel: Thank you so much. Andrew: So when we think about drug therapy to help people with lung cancer, certainly there's surgery often and there's radiation. Where does drug therapy come in? And have your tools that you have been expanding lately? Dr. Patel: We have made tremendous strides in the treatment of lung cancer, particularly in drug therapy, in the past several years. Remember that of the over 200, 000 Americans who will be diagnosed with lung cancer in 2007 the vast majority of them will be treated with chemotherapy at some point in their therapy. A minority of patients have disease that is initially resectable by surgery. About a third of patients have disease that is in the center of their chest, or locally advanced disease, for whom we usually do combination chemotherapy and radiation or combination chemotherapy and surgery. But about 50 percent of people will have. Session 3: Insulin resistance, steatosis and chronic hepatitis C : therapeutic implications Chairs: Thierry Poynard and Vlad Ratziu Insulin resistance and interferon signalling Arun Sanyal, USA ; Impact of insulin resistance and steatosis on sustained virological response Jenny Heathcote, Canada ; Beyond antivirals: management of metabolic risk factors in HCV patients Elisabeth Powell, Australia ; Controversy in management. Should diabetic patients be screened for HCV? Yes: Hashem El Serag USA ; No: Amedeo Lonardo Italy ; Discussion Questions Closing remarks: Perspectives in hepatology and diabetology Vlad Ratziu, France. Inhalational, and GI. Inhalational forms of anthrax infection cause initial nonspecific symptoms including malaise, fatigue, myalgias, low-grade fever, and nonproductive cough, but swiftly progress to severe respiratory distress, fever, shock, and ultimately death.1 Due to its ability to form spores that can be easily stored prior to dispersion, anthrax has been developed as a biological weapon. From a historical perspective, Roger Koch was the first person to culture the bacillus on artificial media in the 1870s. In 1881, Pasteur developed the first anthrax vaccine for veterinary use. The toxin of anthrax was discovered in 1954 by Smith and Keppie.2 The current US vaccine contains protein supernatant purified from B anthracis cultures. There are three major components to the culture filtrate: protective antigen, edema factor, and lethal factor. The protective antigen is most important for the immune response of the vaccine. The contributions of the edema and lethal factors to immunity remain undefined.3, 4 The US vaccine that has been approved by the US Food and Drug Administration since 1970 is administered in six injections. The recommended schedule is 0.5 mL administered subcutaneously at 0, 2, and 4 weeks, followed by boosters at 6, 12, and 18 months. An annual booster is also required to sustain immunity. The vaccine is predominantly composed of protective antigen adsorbed to aluminum hydroxide. The final product contains not more than 2.4 mg of aluminum hydroxide per 0.5-mL dose 0.02% ; , a small amount of formaldehyde 0.02% ; , and benzethonium chloride 0.0025% ; as preservatives. The US vaccine has been administered to military personnel since May 1998. By the end of July 1999, 1, 000, 000 doses had.
Splenic irradiation has been employed in a limited series of patients. Three of seven patients in the Mulligan's series benefited from splenic irradiation 133 ; . Among the seven patients treated by Troussard with 6 to 8 with 1 or 2 fractions over 2 weeks, three relapsed; none of the patients receiving only irradiation died 16 ; . El Weshi reported that even low dose radiotherapy 4 Gy ; may be effective, producing a dramatic reduction in circulating villous lymphocytes, regression of splenomegaly and improvement of cytopenias 134 ; . Radiotherapy seems to be a reasonable and effective treatment option in SLVL when splenectomy is contraindicated and or when pancytopenia is present and likely to give rise to excessive toxicity when chemotherapy is administered. 3 ; Many drugs with different schemes have been administered. There is no univocal convergence when and how to use chemotherapy. Chemotherapy is generally used as first line in more advanced cases. The role of alkylating agents such as chlorambucil or cyclophosphamide is marginal. Few patients benefit when these are used as first-line therapy 6 ; . However, in cases of disease progression, especially after splenectomy, alkylating agents may achieve good response, but seldom complete remission. Mean duration of response in patients treated with alkylating agents alone or in combination with other drugs is 6 months, while 5-year overall survival is 64% 16 ; . The use of purine analogues is more promising, but so far it has been tested in a relatively scarce number of patients. Complete or partial hematologic remission has been achieved with 2-deoxycoformycin 135, 136 ; . Good responses with 2-chlorodeoxyadenosine have been also reported 137 ; , while in other cases only partial responses with high frequency of relapses were obtained 138 ; . Some complete remissions have been achieved with fludarabine as first- or second-line therapy 139-141 ; . 4 ; There is a general consensus, as indicated by the two largest retrospective studies, in considering splenectomy the best first line therapy. A huge symptomatic splenomegaly and or a severe cytopenia are the main indications to perform splenectomy. Long and sustained improvement of cytopenia and relief of abdominal discomfort have been achieved with splenectomy alone. Moreover, in retrospective studies, splenectomized patients have a significantly better overall survival than those treated with chemotherapy 16 ; . However, these data should be cautiously interpreted since this could be, at least partially, an expression of a selection bias, as patients with more aggressive disease are more likely to be treated with chemotherapy. Furthermore, it is intuitive that splenectomy alone cannot reduce extrasplenic lymphomatous infiltrations. Our group has reported a change in the bone marrow infiltration with increase in tumor burden after splenectomy 38 ; . In particular we demonstrated a modification from intrasinusoidal to nodular of the infiltrates in the bone marrow after splenectomy in most patients with SMZL. Conversely, in those patients who did not undergo splenectomy, bone marrow intrasinusoidal infiltration remained stable. Therefore, splenectomy seems to induce important changes in bone marrow infiltration, probably through the lack of microenvironmental homing factors on circulating B-cells. Additional treatment modalities such as single agent rituximab are under investigation 142 ; . Radiolabeled anti-CD20 monoclonal antibodies are currently in the development for the treatment of low-grade B-cell NHLs 143 ; These include the iodine- labeled tositumomab ; and yttriumlabeled anti-CD20 ibritumomab ; . Such approaches possess potential as future therapeutic agents but await investigations and clinical trials. The unexpected regression of SLVL in a HCV patient who was treated with interferon-alfa for symptomatic type II cryogloblulinemia prompted Hermine et al. to evaluate the effect of interferonalfa in eight additional patients 144 ; . Seven out of nine HCV + patients with SLVL had a complete hematologic remission after the loss of detectable HCV-RNA, while none of HCV-negative patients with SLVL had hematologic response to the treatment with interferon. However, the rearrangement of the monoclonal immunoglobulin gene persisted in the blood of the HCV + patients even after a complete hematologic response had been achieved. In the same study Hermine et al. showed that a complete hematologic response occurred after the addition of ribavirin treatment in patients who had a relapse or a partial response to interferon.

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