Improving surgical outcomes for cancer in the United States

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55935/1/20605_ftp.pd

Applications of ISES for snow, ice, and sea state

There will be six facility instruments on the NASA NPOP-1 and NPOP-2 and additional instruments on the Japanese and European satellites. Also, there are the 24 selected NASA instruments that may be flown on one of the platforms. Many of these instruments can provide data that could be very useful for real-time data studies in the snow and ice area. Any one instrument is not addressed in particular, but emphasis is placed on what is potentially possible using the capabilities of some of these instruments

The molecular evolution of surgical oncology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88126/1/22050_ftp.pd

Multidisciplinary cancer clinics: Their time has come

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34521/1/2_ftp.pd

Different cytokine profiles released by CD4+ and CD8+ tumor‐draining lymph node cells involved in mediating tumor regression

We have previously demonstrated that the growth of weakly immunogenic murine sarcomas leads to the induction of immunologically specific preeffector cells in tumor‐draining lymph nodes (TDLN). The in vitro activation of TDLN cells with anti‐CD3 monoclonal antibodies (mAbs) and interleukin‐2 (IL‐2) resulted in the acquisition of effector function as measured by tumor regression in the adoptive immunotherapy of pulmonary metastases. Further studies were performed to characterize the mechanisms associated with in vivo tumor reactivity mediated by activated TDLN cells. By positive selection, CD4+ and CD8+ T cells were purified and activated by the anti‐CD3/IL‐2 method. CD8+, but not CD4+, cells manifested tumor‐specific granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interferon‐γ (IFN‐γ) release in vitro, and elicited tumor regression in vivo. By contrast, only activated CD4+ were found to release significant amounts of IL‐2 in response to tumor antigen but did not mediate tumor regression in vivo. Mixing the two purified populations enhanced the antitumor activity of the CD8+ T cells. In culture, IL‐2 was found to augment the relative amount of tumor‐specific release of GM‐CSF and IFN‐γ by activated TDLN cells. We found that the tumor‐specific release of GM‐CSF and IFN‐γ by activated lymphocytes was strongly associated with the in vivo therapeutic efficacy of these cells. Evidence in support of this included the following: (1) cytokine release of TDLN derived after different durations of tumor growth correlated with tumor reactivity in adoptive transfer studies, (2) cytokine release of T cells derived from different lymphoid organs corresponded with tumor reactivity in adoptive transfer, and (3) in vivo administration of neutralizing mAb to IFN‐γ and GM‐CSF significantly inhibited the antitumor reactivity of TDLN cells. These studies document the contributory roles of IFN‐γ, GM‐CSF, and IL‐2 released by activated CD4+ and CD8+ T cells involved in tumor regression. J. Leukoc. Biol. 61: 507–516; 1997.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142128/1/jlb0507.pd

Tumor-specific granulocyte/macrophage colony-stimulating factor and interferon γ secretion is associated with in vivo therapeutic efficacy of activated tumor-draining lymph node cells

In this study, cytokine release by tumor-draining lymph node cells sensitized in vitro (IVS-TDLN) was examined and correlated with therapeutic efficacy in adoptive immunotherapy. Mice bearing immunologically distinct MCA 207 and MCA 205 sarcoma tumors were utilized in criss-cross experiments. IVS-TDLN obtained from mice bearing 10-day subcutaneous (s. c.) tumors mediated immunologically specific regression of established 3-day pulmonary metastases, but demonstrated non-specific cytolytic reactivity against both tumors in a 4-h 51 Cr-release assay. By contrast, these IVS-TDLN cells were found specifically to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon γ (IFNγ) when restimulated in vitro with irradiated tumor cells. To determine the predictive value of tumor-specific cytokine release with in vivo therapeutic efficacy, a kinetic analysis of antitumor activities of TDLN obtained from animals bearing MCA 207 tumors for increasing lengths of time was performed. IVS-TDLN cells from mice bearing day-7, -10 and-14 s. c. tumors manifested tumor-specific release of GM-CSF and IFNγ, and mediated significant antitumor reactivity in vivo. In contrast IVS-LN cells from day-0 and day-21 tumor-bearing animals did not release significant amounts of GM-CSF and IFNγ, and were not therapeutically efficacious in vivo. Day-4 IVS-TDLN released high levels of GM-CSF and IFNγ non-specifically, and were not therapeutic in adoptive immunotherapy at doses effective for day-7 and day-14 IVS-TDLN cells. In other experiments, IVS cells generated from different lymph node groups in animals bearing 10-day established s. c. tumors were examined and found to have unique profiles of cytokine release. In these studies, the ability of IVS cells to release specifically both cytokines as opposed to one was associated with greater therapeutic efficacy on a per cell basis. Our findings suggest that the tumor-specific releases of GM-CSF and IFNγ are useful parameters to assess the in vivo therapeutic efficacy of immune lymphocytes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46862/1/262_2005_Article_BF01517220.pd

Activation by anti-CD3 of tumor-draining lymph node cells for specific adoptive immunotherapy

Lymph nodes draining progressive tumors contain tumor-sensitized but not functional preeffector T lymphocytes. These cells can acquire antitumor reactivity after stimulation with tumor cells and interleukin-2 (IL-2). We demonstrated here that, in the absence of tumor cells, preeffector cells could be stimulated and expanded by sequential culture with anti-CD3 monoclonal antibody and IL-2. The adoptive transfer of such activated cells mediated immunologically specific reductions of established pulmonary metastases. The therapeutic effects could be enhanced by the administration of IL-2. This activation represents a secondary immune response because effector cells could be generated only from tumor-draining but not from normal or adjuvant-stimulated lymph nodes. Furthermore, treatment of advanced metastases with these cells resulted in prolongation of survival and cure of the disease. Thus, anti-CD3 may serve as a universal reagent for activating tumor-sensitized T lymphocytes for cancer therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29366/1/0000436.pd

The National Cancer Data Base report on cutaneous and noncutaneous melanoma

BACKGROUND This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U. S. within the last decade. METHODS Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated. RESULTS The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment. CONCLUSIONS Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival. Cancer 1998;83:1664-1678. © 1998 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34348/1/23_ftp.pd

Selective incorporation of iododeoxyuridine into DNA of hepatic metastases versus normal human liver

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109868/1/cptclpt1988166.pd