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Biomedical subjects

M A Bookman

Publications and source records attributed to M A Bookman.

67 records · Page 4Linked to original sources
PubMed1986

Expression of MEL-14 antigen is not an absolute requirement for dissemination to lymph nodes after adoptive transfer of murine T lymphocyte clones.

The inability of established antigen-specific murine T lymphocyte clones to recirculate well in vivo has been attributed to loss of the surface glycoprotein gp90MEL-14, which is important for specific adherence to post-capillary high endothelial venules in peripheral lymph nodes (LN). Defective recirculation of clones may contribute to inefficient adoptive immunotherapy when compared with fresh immune spleen or LN populations. To optimize models of adoptive immunotherapy, we sought to improve recirculation of Thy-1.2+, L3T4+ clones by inducing reexpression of MEL-14 antigen (gp90MEL-14). Clones were analyzed after treatment with differentiating agents, incubation in the presence or absence of recombinant interleukin 2 (rIL 2), coincubation in vitro with nonirradiated Thy-1.1 LN or thymus cells, or adoptive transfer into Thy-1.1 hosts. We were unable to demonstrate induction of gp90MEL-14 in any case. However, although clones remained MEL-14 negative, they were able to disseminate widely after subcutaneous adoptive transfer in the presence of clone-specific antigen and rIL 2 into Thy-1.1 mice pretreated with cyclophosphamide. Withdrawal of exogenous rIL 2 was associated with rapid disappearance of clones from all sites. We conclude that murine T cell clones undergo a step in terminal differentiation that precludes surface expression of gp90MEL-14 and that these clones would be unlikely to provide a source of long-lived recirculating memory T lymphocytes. However, under appropriate circumstances it is possible for antigen-specific clones to disseminate widely among host LN and mediate short-term immune responses.

Animals↗
PubMed1979

Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease.

Immunologic characteristics of intestinal mucosal lymphoid cells from patients with inflammatory bowel disease and controls have been compared. Mononuclear cells isolated by enzymatic means from intestinal tissues involved with inflammatory bowel disease were present in greater numbers, with increased proportions of macrophages and B-lymphocytes, particularly cells bearing intrinsic membrane immunoglobulin G. Synthesis of immunoglobulin G, measured by radioimmunoassay, was increased tenfold in inflammatory bowel disease, while immunoglobulin A synthesis per 10(6) cells was unchanged. "Null" or K-lymphocytes were absent from all populations, and antibody-dependent cellular cytotoxicity (a K-cell-mediated function) was not demonstrable. Taken together, the results fail to support a role for antibody-dependent cellular cytotoxicity or a defect in secretory immunoglobulin A, but rather focus attention upon possible forms of immunoglobulin G-mediated tissue damage in the pathogenesis or perpetuation of inflammatory bowel disease.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Isolation and functional characterization of human intestinal mucosal lymphoid cells.

Viable suspensions of human colonic mucosal lymphoid cells have been prepared by sequential treatment of tissue with dithiothreitol, EDTA in calcium- and magnesium-free salt solutions, and purified collagenase. The intestinal lymphocyte population, in comparison with that of peripheral blood, had greater numbers of bone marrow-derived cells, particularly cells bearing membrane IgA; showed spontaneous association with macrophages; underwent rapid rosette formation with sheep erythrocytes; and demonstrated increased in vitro synthesis of immunoglobulin. Total thymus-derived cells were equal in the two populations. Decreases were found in "null" cell numbers, in cells bearing membrane IgD and IgM, and in responsiveness to phytohemagglutinin. Macrophage/monocytes in the intestinal population were increased in size, granularity, motility, sustained glass adherence, and phagocytic activity. Human intestinal lymphoid cells appear to constitute a cell population that is more "mature" and/or "activated", in comparison with the lymphoid cells of peripheral blood. The method of preparation should lend itself to the study of inflammatory bowel disease, gastrointestinal cancer, and the intestinal secretory immune system.

Antibody Formation↗
PubMedDate not supplied

Medical management of early-stage breast cancer.

With improved screening and education, a greater proportion of breast cancer is detected at an early stage. Although the prognosis for many of these patients is excellent following definitive local therapy alone, some subsets of node-negative patients have a 30% chance of eventually developing metastatic disease that will be incurable with current therapy. Thus, an increasing proportion of early-stage patients are being offered some form of adjuvant therapy, with the expectation of improved relapse-free survival, and possibly improved overall survival. Efforts have been made to base the selection of patients for adjuvant therapy on specific prognostic factors. Meanwhile, the scope and complexity of putative prognostic factors continues to widen, and now includes such items as the presence of occult microscopic metastases, DNA ploidy and proliferative fraction, cytogenetic abnormalities, oncogene expression, growth factor receptors, and expression of hormonally regulated proteins. In addition, there is now a considerable range of options with regard to the composition, dose intensity, and sequence of multimodality therapy. Data regarding the classification, significance, and interpretation of prognostic factors is reviewed together with the development, current status, and recommendations regarding adjuvant therapy for patients with early-stage breast cancer. For 1991, the National Cancer Institute (NCI) has estimated that 175,000 new cases of breast cancer will be diagnosed in American women. It is also estimated that 44,500 women will die of breast cancer. Unfortunately, the age-adjusted death rate from breast cancer has shown no overall change from 1930 through 1987. However, effective screening techniques continue to identify an increasing percentage of early-stage tumors, which should exceed 50% of all new tumors in 1991. Ultimately, our understanding of environmental and genetic risk factors may identify new ways to reduce the impact of this disease. In the interim, development and application of effective systemic adjuvant chemotherapy and hormonal therapy has become increasingly important. There is no question that a greater proportion of patients with less extensive disease are now being offered some form of adjuvant therapy. Meanwhile, selection of patients for adjuvant therapy, and choice among specific adjuvant regimens, has remained controversial. Analysis of multiple prognostic factors is performed not only in the context of cooperative investigational trials, but more often in the offices of individual physicians caring for individual patients. Tumor biopsies can now be routinely sent to specialized laboratories for performance of complex assays with potential prognostic information, although interpretation of these results with reference to a specific patient is often uncertain.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMedDate not supplied

Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel versus cisplatin and paclitaxel (GOG158) and an update on GOG0182-ICON5.

Mature results from GOG158 have clearly established carboplatin and paclitaxel as an effective and well-tolerated standard regimen, providing a basis for the reference arm in GOG0182-ICON5, an ongoing multiarmed phase III trial of the Gynecologic Cancer InterGroup (GCIG) evaluating the incorporation of newer cytotoxic agents. Results from GOG158 will be reviewed, including an analysis of second-look surgical outcomes, followed by an update on the current status of GOG0182-ICON5.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs. cisplatin and paclitaxel (GOG 158) and an update on GOG0 182-ICON5.

Mature results from GOG158 have clearly established carboplatin and paclitaxel as an effective and well tolerated standard regimen, providing a basis for the reference arm in GOG0182-ICON5, an ongoing multiarmed phase III trial of the Gynecologic Cancer InterGroup (GCIG) evaluating the incorporation of newer cytotoxic agents. Results from GOG158 will be reviewed, including an analysis of second-look surgical outcomes, followed by an update on the current status of GOG0182-ICON5.

Adult↗
PubMedDate not supplied

Is there still a role for hormonal therapy?

Ovarian cancer arises from the specialized surface epithelium, which routinely expresses receptors for reproductive hormones and growth factors. However, as a group, ovarian tumors are less responsive to hormonal therapy than either breast or endometrial cancer. The complex factors that govern hormonal response and associated molecular interactions are under intensive investigation, with the generation of new hypotheses that merit clinical evaluation. As such, it is reasonable to consider a number of potential hormonal interventions related to the prevention and treatment of ovarian cancer.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Standard treatment in advanced ovarian cancer in 2005: the state of the art.

What are standards? The oncology community expends considerable effort to review the results from definitive treatment studies and define recommendations for future studies, as well as standards of care for the community and patients who are not participating in clinical trials. This is a thoughtful and well-intentioned process but subject to considerable bias due to limitations in the data and/or their interpretation. While ovarian cancer is highly responsive to platinum-based therapy after initial cytoreductive surgery, there is a substantial risk of recurrence, which is accompanied by the emergence of drug-resistant disease. Better treatments with improved long-term outcomes are needed. From this perspective, standards can help to provide a baseline for assessing gaps in our current knowledge and defining priorities for future clinical trials. While not an exhaustive review, this study will focus on key clinical concepts that are guiding ovarian cancer research and treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Gemcitabine monotherapy in recurrent ovarian cancer: from the bench to the clinic.

Gemcitabine (2'2'-difluorodeoxycytidine [dFdC]) is a synthetic analog of deoxycytidine with two fluorine atoms at the 2' position of the carbohydrate. As a hydrophobic molecule, dFdC competes for intracellular access via membrane-associated nucleoside transporter proteins. Following intracellular transport, dFdC is phosphorylated sequentially by deoxycytidine kinase to gemcitabine triphosphate, which inhibits ribonucleotide metabolism, hinders DNA processing, and increases accumulation of intrastrand adducts and interstrand cross-links, thereby leading to a G1 block in the cell cycle. dFdC monotherapy has been extensively evaluated at doses of 800-1250 mg/m2. dFdC is generally well tolerated, with the most frequently occurring dose-limiting toxicities being hematologic, noncumulative, and easily managed by dose alteration. Several studies involving treatment of recurrent ovarian cancer patients with dFdC monotherapy, most of whom had platinum-resistant disease and/or prior exposure to paclitaxel, led to overall response rates of 14-22% and a median duration of response of 4.0-10.6 months. An additional one third of the participants experienced stable disease for an overall clinical benefit in approximately one half of the treated patients. Tumor cells with a multidrug resistance phenotype have increased sensitivity to dFdC (collateral sensitivity). As dFdC is unaffected by platinum resistance, and not susceptible to classic multidrug resistance, it could be particularly beneficial to administer following treatment with agents that induce multidrug resistance. Integration of dFdC with platinum and/or radiation should also be investigated.

Antimetabolites, Antineoplastic↗