PubMed Health⌕ Search

Biomedical subjects

R E Pollock

Publications and source records attributed to R E Pollock.

90 records · Page 5Linked to original sources
PubMed1990

Preoperative chemotherapy for soft-tissue sarcomas of the extremities.

Forty-six patients with extremity soft-tissue sarcomas were treated with a mean of 4.4 cycles of preoperative adriamycin-based combination chemotherapy, followed by definitive local surgery and radiotherapy. All tumors were larger than 5 cm and of histologic type having significant risk of metastasis. Eighteen patients (40%) had an objective clinical response to the chemotherapy, while 27 patients (60%) did not respond. Patients with tumors responsive to chemotherapy had significantly improved overall survival (median 60 + months versus 32.7 months; p = 0.02), continuous disease-free survival (median 60 + months versus 15.1 months; p = 0.04), and distant metastasis-free survival (median 60+ months versus 28.5 months; p = 0.006) compared to the nonresponding patients. Tumor response to preoperative chemotherapy provides strong prognostic information and identifies a subgroup of patients most likely to benefit from chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Immunologic and clinical aspects of natural killer cells in human leukemia.

We have studied peripheral-blood, splenic and bone marrow natural killer (NK) activity in patients with leukemia. These studies demonstrated that leukemic patients displayed defective NK activity in all of these tissues. However, NK defect could be corrected by culture of effector cells with interleukin-2 (IL-2). The phenotypic analysis of IL-2 cultures showed clearly the heterogeneity of lymphocyte subsets. The characterization studies demonstrated that CD56+, CD3- NK cells manifested most potent lysis of leukemia, CD56+, CD3+ T cells mediated some, but low, antileukemia activity and CD56-, CD3+ T lymphocytes were devoid of cytotoxicity.

Bone Marrow Cells↗
PubMed1989

Surgical stress impairment of murine natural killer cell cytotoxicity involves pre- and postbinding events.

NK cell cytotoxicity may provide an important first line of defense against the implantation of circulating tumor emboli. Previously we reported that murine hind limb amputation induces a rapid and marked impairment of perioperative NK cell cytotoxicity that is associated with increased metastatic activity compared to unmanipulated tumor-bearing controls. Because tumor emboli are systemically discharged in patients undergoing solid tumor resection, we thought it pertinent to begin examining the mechanism underlying the perioperative impairment of murine NK cell cytotoxicity. Studies presented in this report suggest that the mechanism of impairment is multifactorial and includes the surgical stress-induced expansion of splenic erythroblasts that successfully compete with NK cells for YAC-1 target binding sites. In addition, although there is no surgically mediated decrease in splenic NK cell content (as defined morphologically, phenotypically, and functionally), there is an acute decrease in maximal NK cell recycling capacity. An accurate understanding of the mechanisms mediating perioperative impairment of NK cell cytotoxicity may be important in the future development of NK-specific perioperative immunomodulation strategies.

Amputation, Surgical↗
PubMed1989

Cancer-induced immunosuppression: implications for therapy?

Cancer-induced immunosuppression can be caused by a variety of effects. These include factors produced by the host in response to the presence of tumor or factors elaborated by the tumor itself. Disseminated tumor can lead to host debility with associated anergy. Some immunosuppressive effects are due to the manner in which the host processes (or fails to process) the tumor as an antigenic stimulus. Lastly, antitumor treatments can have a detrimental impact on host antitumor immunity. Recent research findings from our laboratories implicate surgical stress effects and tumor-mediated production of growth factors such as transforming growth factor beta (TGF-beta) as being important causes of host immune impairment. An accurate understanding of the mechanisms underlying host antitumor immune impairment will be critical in the successful development of immunotherapy strategies for use in the surgical oncology patient.

Animals↗
PubMed1988

Tumor burden impairment of murine natural killer cell cytotoxicity.

Natural killer (NK) cells may be important in the control of circulating tumor emboli. Because of this, the suppression of natural killer cell cytotoxicity (NKCC) observed with progressive tumor burden is a concern relative to the treatment of solid tumors. Our study examines the interplay between tumor progression, elaboration of metastases, and NKCC. Mice inoculated with Lewis lung carcinoma (3LL) cells developed visible primary tumors by day 6 of tumor bearing. This tumor burden appeared to be associated with a progressive decrease in NKCC beginning after day 6 of tumor bearing. Significant splenomegaly was observed beginning by day 12. Rapidly reproducing tumor cells take up 125I-labeled 5-iodo-2'-deoxyuridine (125I-IUDR) in lieu of thymidine more readily than normal cells. Intraperitoneal injection of the labeled IUDR allowed the identification of possible pulmonary metastatic activity earlier in the tumor progression sequence than has previously been possible using standard staining procedures. A significantly increased level of lung 125I-IUDR uptake was observed in the lung beginning after day 6 of tumor bearing; this increase in 125I-IUDR uptake began at the same time as the tumor burden impairment of NKCC. Successful implantation of tumor emboli may occur very early in experimental tumor burden systems, when measurable antitumor immune effector mechanisms are not yet massively suppressed. Antitumor immunotherapy programs may therefore need to be targeted to these earlier points of tumor bearing.

Animals↗
PubMed1987

Effect of surgical stress on murine natural killer cell cytotoxicity.

Natural killer cell cytotoxicity (NKCC) against tumors may be important in preventing in vivo solid tumor dissemination. Multiple animal models demonstrate increased rates of tumor dissemination after surgical stress; previously, we have observed that surgical stress impairs murine NKCC. Because of the importance of surgery in the control of solid tumors, it appeared valuable to examine the mechanism underlying surgical stress impairment of NKCC. The results of this study demonstrate that postsurgical suppression of NKCC begins as early as 2 hr after murine hind limb amputation, reaches nadir at 4 days, and does not recover to control level until postoperative day 12. Anesthetic treatment alone does not cause comparable NKCC suppression. The suppression of NKCC accompanied changes in both splenic size and morphology. The immune suppression was observed in multiple compartments including peripheral blood, bone marrow, and spleen. Mixing experiments demonstrated that surgical stress per se generated a suppressor cell population affecting NKCC. The observed suppression apparently required cell-to-cell contact, because supernatants from 4 and 18 hr cultures of suppressor cells did not cause suppression. The observed suppression was prevented by perioperative treatment with the pyrimidinone analog 2-amino-5-bromo-6-phenyl-4-pyrimidinol. These preclinical observations point to the future prospect of NK-specific perioperative immunotherapy that may help prevent possible tumor dissemination from occurring at the time of surgery.

Animals↗
PubMed1987

Lysis of fresh solid tumor targets in the presence of Con A is mediated primarily by Leu 7+ peripheral blood T lymphocytes: blocking by the anti-CD3 monoclonal antibody and comparison with recombinant interleukin 2-induced lysis by natural killer cells.

We investigated the lysis of fresh human solid tumor cells by peripheral blood T lymphocytes in the presence of lectins and anti-CD3 monoclonal antibodies (mAb). Addition of certain lectins (Con A, PHA, or WGA) directly into the 4-hr 51Cr-release assay caused significant lysis of (P less than 0.001) noncultured solid tumor targets by enriched populations of granular lymphocytes (GL). Significant levels (P at least less than 0.001) of Con A- or PHA-dependent solid tumor lysis by GL-enriched lymphocytes were observed in 32 of 39 donors (82%) and 14 of 20 donors (70%), respectively. In contrast, the addition of other lectins (PNA, PWM, or LPS) or anti-CD3 mAb did not cause cytotoxicity. The levels of Con A-dependent lysis were comparable to those of interleukin 2 (IL-2)-induced lysis by Leu 11b+ natural killer (NK) cells. The presence of lectins at the effector phase, but not of recombinant IL-2 (rIL-2), was required for the lysis of solid tumor targets. Both Con A-dependent and rIL-2-induced lysis were totally inhibited by treatment of the effector cells with the lysosomotropic agent L-leucine methyl ester (LeuOMe). Effector cells responsible for Con A-dependent lysis of solid tumors expressed T3 (CD3), T8 (CD8), and Leu 7 antigens, but lacked T4 (CD4) and Leu 11 (CD16) antigens as determined by both negative and positive cell selection studies. Con A-dependent lysis was inhibited at the effector phase by anti-CD3 (OKT3 or anti-Leu 4) or anti-CD2 (OKT11) mAb. On the basis of their phenotype (Leu 7+ CD3+ CD8+ CD16-), we hypothesize that these effector cells may contain a population of cytotoxic T cells (CTL) generated in vivo against autologous modified cells that can lyse fresh solid tumor target cells under conditions where the recognition requirements for the CTL are bypassed by lectin approximation.

Antibodies, Monoclonal↗
PubMed1985

A surgical oncology perspective on AIDS.

During the summer of 1981 reports of unusual opportunistic infections among male homosexuals first began to appear in the literature and by December 1983, 3000 cases has been reported to the Center for Disease Control in Atlanta, Georgia. Homosexual and bisexual men comprise 71% of the reported cases, while 17% are known intravenous drug users, and the remaining 12% made up of persons with other risk factors. Approximately 80% of AIDS patients with Kaposi's sarcoma have identifiable gastrointestinal lesions. Specific risk factors for Kaposi's sarcoma in AIDS patients have not been exclusively identified, but it is thought that repeated sexual involvement with multiple partners exposes the victim to the immunosuppressive effect of cytomegalovirus and allogenic sperm, which may in turn impair lymphoid cells. The immunological abnormalities associated with AIDS have included striking changes in T-cell ratios, with more profound changes in the Kaposi-AIDS groups. Increases in IgG, decreased antibody production by B-cells to challenge antigen, decreased B-cell proliferative responses to B-cell mitogens, abnormalities in macrophage function, and increased serum thymosin levels have been found. Various opportunistic infections afflict the patient with AIDS. Antimicrobial therapy, various interferons, interleukin-2, and immunomodulation with thymosin have all been used without much success. The distribution and transmission of AIDS parallels hepatitis B virus infection which is transmitted sexually and parenterally. On the whole the same precautions as for hepatitis B should be taken for AIDS. Health care personnel treating patients with AIDS should also wear masks and eye protection against the splatter of body fluids and secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1984

Surgical stress-mediated suppression of murine natural killer cell cytotoxicity.

Natural killer cell-mediated cytotoxicity (NKCC) is one of several possible immune defense mechanisms that may protect against the development of solid-tumor metastases. We have demonstrated that in vitro NKCC can be significantly impaired by both surgical stress and progressive tumor burden. Female C57BL/6 mice received a hindfoot amputation under anesthesia with Nembutal i.p. Twenty-four hr later, amputated and control groups were sacrificed, spleens were harvested, and cytotoxicity assays were performed using 51Cr-labeled Yac-1 lymphoma target cells. In amputated animals, in vitro NKCC was significantly impaired at four effector:target ratios, decreasing by as much as 59%. Nembutal treatment alone caused no significant changes in in vitro NKCC compared to untreated controls. Tumor burden was studied by inoculating the hindfoot pads of C57BL/6 mice with 5 X 10(5) Lewis lung tumor cells. Animal groups were sacrificed 24 hr, 1 week, and 2 weeks after tumor inoculation, and the 51Cr release assay was performed. One day and 1 week of tumor burden mildly stimulated NKCC in vitro; after 2 weeks of tumor burden, when lung metastases were detectable, in vitro NKCC was almost totally suppressed compared with non-tumor-bearing controls. Animals bearing tumor for 1 week and then given amputations showed significantly impaired NKCC in vitro. In vivo, identical animals bearing tumor for 1 week and then given amputations on sacrifice 1 week later were found to have a 71% incidence of lung metastases compared with 38% tumor-bearing unstressed controls. Surgical stress and progressive tumor burden independently and codependently impair NKCC in vitro; this may possibly contribute to the hypermetastatic response observed after surgical stress in this in vivo animal model.

Amputation, Surgical↗
PubMedDate not supplied

Molecular determinants of soft tissue sarcoma proliferation.

Soft tissue sarcoma is an extremely rare malignant disease that includes more than 15 distinct histologic subtypes. While all share a propensity for metastasis to the lungs, the clinical presentation and pattern of spread for the specific subtypes are remarkably viable. Little is known about the etiology of soft tissue sarcoma other than several well described epidemiological associations between ionizing and other toxic agents and several of the soft tissue sarcoma histologic subtypes. The key to understanding the etiologic factors driving soft tissue sarcoma proliferation and dissemination lies in understanding the molecular mechanisms underlying these oncologic processes. Progress in this regard has been difficult because of the rarity of this disease. This report reviews the current state of knowledge for three of the most important considerations involving the molecular etiology of soft tissue sarcoma: growth factors and their receptors, nuclear and cytoplasmic oncogenes, and tumor suppressor genes. As we learn more about these molecular mechanisms leading to proliferation and dissemination of soft tissue sarcoma, molecularly based genetic therapies will become a reality for this all too devastating, albeit rare, disease.

Cell Division↗
PubMedDate not supplied

Myofibroblastoma of the axilla.

A mass in the axilla of a 47-year-old woman was biopsied and resected. The mass was composed of a loosely distributed population of spindle cells that were immunoreactive for smooth-muscle actin. Ultrastructurally, the cells possessed abundant endoplasmic reticulum, and some contained peripheral smooth muscle myofilaments, establishing that they were myofibroblasts. Mitotic activity was sparse, there was no cytologic atypia, and by flow cytometry the tumor was diploid with a low S phase. A diagnosis of myofibroblastoma was favored, although the possibility of a low-grade sarcoma could not be excluded. There has not been any indication of recurrence over a 4-month period of follow-up.

Axilla↗
PubMedDate not supplied

Advances in the understanding of human soft tissue sarcomas: molecular biology and therapeutic strategies (Review).

Soft tissue sarcomas comprise a group of exceedingly rare and histologically diverse malignancies. A multidisciplinary approach utilizing surgery, radiation therapy, and chemotherapy has evolved to address the challenge of effective treatment. Pertinent to this clinical goal are efforts to understand the molecular mechanisms underlying the etiology, proliferation, and metastatic phenotype of these tumors. This review describes the specific research efforts of our laboratory, which focus on the role of tumor suppressor genes and angiogenic factors as drivers of malignant behavior in soft-tissue sarcomas. By enlarging our knowledge of basic sarcoma tumor biology, it may be possible to identify important molecular mechanisms that can guide the design of future molecularly based therapies for this disease.

Cell Division↗
PubMedDate not supplied

Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field.

PURPOSE: The use of further radiotherapy among patients with soft tissue sarcoma that recurs in a previously irradiated area is controversial. Presented is a review of our 7-year experience with brachytherapy for recurrent soft tissue sarcoma. METHODS: A retrospective review was performed of 26 patients who underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated field. After-loading brachytherapy catheters were placed at the time of surgical extirpation of the sarcoma within a single-plane implant by use of 1-cm intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until the fifth to seventh postoperative day to allow initial wound healing. The prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and the dose was specified at 0.5 cm from the plane of the implant. The anatomic locations treated included lower extremity (N = 10), upper extremity (N = 7), trunk (N = 7), and head and neck (N = 2). RESULTS: Total tumor extirpation, confirmed by negative frozen section margins, was accomplished in all cases. The mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy +/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue transfer flap was placed over the bed of resection in 13 cases. Complications occurred in five patients including, three with wound breakdown, one with osteonecrosis, and with neuralgia. Operative intervention was required in four of the five patients with complications; each of the patients requiring operative intervention for wound-related complications had undergone primary wound closure without tissue transfer. Recurrence of disease occurred in 13 patients: nine local and four distant metastases. The median follow-up was 16 months (range, 2 to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease-free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%, respectively. CONCLUSION: Re-irradiation of recurrent soft tissue sarcoma by brachytherapy in conjunction with resection can be performed with acceptable complication rates. Local control can be achieved for the majority of patients who would otherwise require more radical surgical procedures.

Adult↗