No description available.

No description available.

A functional immune system is a potential barrier to tumor growth and progression. Cancer is caused, in part, by the loss of immune surveillance leading to the inability of the immune system to destroy the cancer cells. Macrophages (Mfs) are essential cellular components of the immune system; they influence immune responses in diverse and fundamental ways. As a consequence, Mfs present targets for tumors to evade, thereby enhancing tumor survival and growth. An interaction between CD40 on Mfs and CD40L on T cells is required for cell-mediated inflammatory responses. The CD40/CD40L interaction is bi-directional; suppressed expression of either protein by the tumor will prevent activation of both Mfs and T cells. We showed that tumor growth suppresses T-cell CD40L expression. Decreased CD40L expression disrupted Mf activation pathways, leading to impaired production of immunostimulatory cytokines, interleukin (IL)-12 and IL-18 by tumor-bearing host (TBH) Mfs. Disruption of CD40L expression, via dysregulation of IL-12 and IL-18 production, impeded T-cell interferon (IFN)-g production, which in turn exacerbated Mf dysfunction. We showed that IFN-g induced interferon consensus sequence binding protein (ICSBP) expression is impaired in TBH Mfs due to tumor cell-derived TGF-b and, to a lesser extent, IL-10. ICSBP induces CD40L, IL-12, and IL-18 expression. Disruption of the CD40/CD40L interaction via lowered CD40L expression generates an immunosuppressive loop that may be a strategy for tumor survival and growth. This was demonstrated by impaired cytotoxicity; via impaired tumor necrosis factor (TNF)-a and nitric oxide (NO) production by TBH Mfs against Meth-KDE tumor cells. Collectively, these studies show that multiple antitumor mechanisms could be enhanced by restoration of CD40L expression. / Master of Science

Call number: LD2668 .T4 1962 V47

The spontaneous tumoricidal ability of pulmonary alveolar macrophages (PAM) isolated from C57B1/6 mice bearing either a metastatic or a nonmetastatic cloned variant of Lewis lung carcinoma (LLC) was examined in vitro. During the early weeks of tumor development the cytotoxicity mediated by macrophages was enhanced in the tumor-bearing mice, especially in the metastatic tumor bearers. Later in tumor progress (week 4) the spontaneous cytotoxicity of both groups typically declined to levels less than those of normal macrophages. Experiments were performed to determine if macrophages could be activated further in vitro by incubation in a mixture of lymphokine and lipopolysaccha ride. The macrophages from the metastatic tumor bearers were consistently activated in vitro. However, macrophages isolated from mice bearing large tumors and whose spontaneous cytotoxicity was suppressed could not be activated.The secretion of prostaglandin E2 (PGE2) by macrophages at different times during tumor development was measured to determine if PGE2 levels corresponded with the ability or inability of macrophages to kill tumor cells. Secretion of PGE2 typically corresponded with the capacity to kill rather than with an inability to kill target cells. Similarly, the production of PGE2 by macrophages was not responsible for the decline in the ability of macrophages to kill tumor cells.These results suggest that PAM are activated to be cytotoxic during the period when pulmonary metastases are developing. The successful establishment of these metastases does not appear to depend on the capacity of the tumor to suppress alveolar macrophage cytotoxicity. / Department of Biology

Thesis (M.S.)--University of Michigan, 1960.

No description available.

No description available.

Cystic nephromas are rare, multiloculated cysts on the kidneys that occur mostly in early childhood. They are considered to be on the same spectrum as cystic partially differentiated nephroblastomas (CPDN) and Wilm’s tumors (WT). They are mostly benign, however, when cystic nephroma is associated with DICER1 mutation, the patient is predisposed to other, more aggressive tumors. DICER1 mutations are not seen in CPDN or WT, so molecular evaluation can help differentiate between them if the histology is unclear. The DICER1 gene is on chromosome 14 and it functions to make microRNA that attaches to mRNA and represses protein synthesis. Mutations of this gene predispose patients to neoplasms on various organs such as the lung, kidneys, ovaries, and thyroid. The data in this case report was gathered via direct patient care and patient chart review. An 18-month-old previously healthy female was hospitalized for a newly diagnosed abdominal mass found on palpation during a well child evaluation. The ultrasound revealed a 9 cm cystic mass on the left kidney and the patient was subsequently sent to St. Jude Children’s Research Hospital. Further evaluation via CT scan has shown a large left renal mass that invaded the ureter and bladder, as well as enlarged lymph nodes in the left suprarenal space and a single 3mm right pulmonary nodule. At this time, cystic Wilm’s tumor was considered and the patient underwent a left radical ureteronephrectomy with lymph node sampling. Cytology report of the pelvic fluid had some inflammatory cells, but no tumor cells were seen in the sample. All of the sampled lymph nodes were also negative for tumor cells. The histological analysis of the mass revealed multiple cystic cavities separated by septa. No blastemal elements (WT1 immunostain was negative) or distinct solid areas were identified, which made the diagnosis of cystic Wilm’s tumor unlikely. The diagnosis of cystic nephroma (CN) vs cystic partially differentiated nephroblastoma (CPDN) is determined histologically by looking at the components of the septa – which, in this case, due to a marked inflammatory infiltrate expending the septa, made the morphology be more congruent with CPDN. Molecular testing of the tumoral tissue identified two DICER1 mutations (DICER1 frameshift mutation and DICER1 D1709E). Patient was subsequently diagnosed with Cystic Nephroma Stage I and further surveillance will be continued to monitor for more neoplasms associated with this mutation. This case highlights a rare disorder that predisposes patients to multiple neoplasms. Histology may not always be sufficient in determining the diagnosis, especially in differentiating CN from CPDN. Molecular evaluation may be helpful for the initial diagnosis and in order to provide adequate genetic counseling. Clinicians should be aware of DICER1 syndrome so they can adequately survey the at-risk patients for a range of benign and malignant neoplasms.

Mouse mammary tumor is a common form of cancer used for experimental purposes. It is relatively resistant to chemotherapy. This investigation is designed to test the effect of heparin, a naturally occurring anticoagulant, on tumor growth using a genetically uniform laboratory animal.