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Biomedical subjects

Marc K Wallack

Publications and source records attributed to Marc K Wallack.

11 recordsLinked to original sources
PubMed2006

Expression of melanoma-associated antigens in human dendritic cells pulsed with an interleukin-2 gene encoded vaccinia melanoma oncolysate (rIL-2VMO).

Dendritic cells (DCs) possess the unique abilities to initiate a primary immune response and to present antigens to naïve T lymphocytes. Recently, there has been a rapidly growing interest in the use of DCs in active specific immunotherapy (ASI) for the treatment of patients with cancer. In the present study, we determined the ability of DCs to express Melanoma-Associated Antigens (MAAs) from a polyvalent Melanoma Vaccine (DC-MelVac; Patent #11221/5) developed in our facility. The vaccine consists of a recombinant IL-2 gene-encoded vaccinia melanoma oncolysate (rIL-2VMO) derived from an established human melanoma cell line. Our results show that r-IL2VMO-pulsed DCs express MAAs presented by the Mel-2 melanoma cell line oncolysate used in this study. We believe that these promising results will prove useful as an active specific immunotherapeutic agent for patients with Stage III melanoma.

Antigen-Presenting Cells↗
PubMed2005

September 11, 2001, revisited: a review of the data.

HYPOTHESIS: The September 11, 2001, World Trade Center (WTC) attack was a disaster of epic proportion in New York City, NY. It was unprecedented in terms of the number of people who were killed in the bombings, as well as in terms of the volume of patients received at local (New York City) hospitals. The strain on local emergency medical services, hospitals, and the citywide trauma system is still felt today as the hospitals, physicians, and agencies involved struggle to train for similar events that may occur in the future, cope with the psychological and social aftermath, and even pay for the response to the bombing. The objective of this review of the data was to determine the major causes of morbidity (ie, hospital visits) during the hours immediately after the September 11, 2001, WTC attack, as well as to detail the costs involved in the medical response to a disaster of this scale and to identify some lessons learned with respect to the hospital's response to an event of this magnitude. DESIGN: Review of records and cost data submitted by Saint Vincent's Hospital, Manhattan, NY, to the state of New York and federal sources for financial relief from the September 11, 2001, WTC attack. SETTING: Saint Vincent's Hospital is an academic medical center of New York Medical College and a New York City-designated level I trauma center. PATIENTS: All medical records for the patients registered at Saint Vincent's Hospital on September 11, 2001, after 8:50 am were reviewed. RESULTS: The major cause of morbidity for the September 11, 2001, patients was smoke inhalation (30.0%); followed closely by chemical conjunctivitis and corneal abrasions (16%); lacerations, abrasions, and soft-tissue injuries (15.5%); isolated orthopedic complaints (12%); and psychiatric complaints (10%). Multiple-trauma patients were 3% of the patients seen. There were 5 fatalities at Saint Vincent's Hospital. CONCLUSIONS: The WTC disaster was a source of major morbidity and mortality to the people of New York City. The possibility that Saint Vincent's will again serve in that role is in the forefront of the minds of everyone involved in updating our contingency plan.

Academic Medical Centers↗
PubMed2005

Multilayer reconstruction of abdominal wall defects with acellular dermal allograft (AlloDerm) and component separation.

Multiple techniques have been employed for the repair of abdominal incisional hernias with varying rates of success. Primary fascial apposition and prosthetic implantation have been associated with high rates of secondary recurrence, infection, and other complications, often due to insufficient alleviation of tension and implant intolerance. This study evaluates the repair of incisional and recurrent abdominal hernias with multilayered acellular dermal allograft (AlloDerm; LifeCell Corporation, Branchburg, NJ) and musculofascial separation. Patients with incisional or recurrent abdominal hernias were treated between January 2003 and March 2004. The surgical technique involved musculofascial release of the external oblique, followed by a double-layer implantation of dermal allograft. The primary allograft layer was placed as an "underlay" interposition, sutured under moderate tension beneath the fascial edges of the defect. When minimal tension remained, the native fascial margins of the defect were directly repaired. A second allograft layer was then placed and sutured to the superficial aspect of the ventral fascia to complete the repair. Data were reviewed retrospectively. Sixteen patients were treated. There were 10 males and 6 females, mean age 56 years (range 44--72 years). Fifteen patients (94%) had previous hernia repair procedures, and 6 patients (38%) had undergone 2 or more previous procedures. Nine patients (56%) were treated with hernia site infections or prosthetic exposure. Mean follow-up is 16 months (range 9 to 23 months). There were 2 seromas (13%). One patient (6%) developed a wound dehiscence with allograft exposure that healed by secondary intention. There were no recurrences. By minimizing tension and providing a durable biocompatible matrix for support, component separation with bilaminar acellular dermal allograft should be considered for the repair of complex and recurrent ventral hernias.

Adult↗
PubMed2002

Therapeutic effect of colon tumor cells expressing FLT-3 ligand plus systemic IL-2 in mice with syngeneic colon cancer.

Flt-3 ligand (FL) and interleukin-2 (IL-2) have been shown to enhance individually the antitumor response against several cancers. Therefore, treatment with a combination of FL gene-transduced tumor cell plus soluble IL-2 was studied in a murine colon adenocarcinoma model. The human full-length FL cDNA was cloned from FL-expressing cell line AML-193 by reverse transcription-polymerase chain reaction (RT-PCR). CC-36 colon tumor cells were transduced with the FL gene (CC-36-FL). In vivo and in vitro secretion of FL from CC-36-FL was confirmed by enzyme-linked immunosorbent assay (ELISA). Moreover, enhancement of dendritic cells in vivo was evaluated in mice transplanted with CC-36-FL. The therapeutic efficacy of CC-36-FL plus systemic IL-2 was tested using six groups ( n=12-13/group) of 10-week-old male Balb/c mice transplanted with 10(3) CC-36 tumor cells. Mice were treated subcutaneously with 10(6) irradiated CC-36 cells, 10(6) irradiated CC-36 cells+IL-2, 10(6) irradiated CC-36-FL cells, 10(6) irradiated CC-36-FL+IL-2, or IL-2 alone on days 4, 10 and 18 after tumor transplantation. A group of mice with no treatment served as a control. All of the treatment injections were performed subcutaneously in the left flank. IL-2 (2 x 50,000 IU) was administered intraperitoneally in 3-day cycles (days 4-6, 10-12, 17-19). Tumor growth was determined by measuring the tumor diameter. A survival experiment was performed with the same treatments, and mice were observed for survival for 100 days. The group of mice treated with the combination of CC-36-FL+IL-2 showed a significant reduction in tumor burden when compared to the no treatment group and the other control treatment groups ( P<0.05). Similarly, the group of mice treated with CC-36-FL+IL-2 displayed significant survival when compared with the other control groups (P<0.05). In Balb/c mice, the CC-36-FL plus systemic IL-2 therapy significantly decreased the tumor burden and increased the survival rate when compared to mice treated by control therapies or mice that received no treatment.

Animals↗
PubMed2002

The state of general surgery residency in the United States: program director perspectives, 2001.

HYPOTHESIS: Current demographic patterns and lifestyle factors of general surgery residents may contribute to recent changes in recruitment patterns. DESIGN: Survey addressing the characteristics of general surgery residency, including demographic data, 3-year recruitment and retention trends, and working conditions of general surgery residents. PARTICIPANTS: A convenience sample of all residency program directors in attendance at the 2001 Surgical Education Week was given the opportunity to voluntarily complete the survey. RESULTS: A total of 109 program directors responded to the survey. Women constitute 25% of all current general surgery residents: 66% of the program directors perceived a decline in the number of applicants for general surgery residency. Recruitment patterns differ significantly between small (< or =4 categorical residents per year) and large (>4 categorical residents per year) residency programs. Residents at large programs averaged a 95-hour workweek, whereas those at small programs averaged an 88-hour workweek (P =.01). The mean 1-year attrition rate for general surgery residents was 20.2% in 2000, and attrition showed no relationship to program size, gender composition, or working conditions. CONCLUSIONS: Women remain underrepresented in general surgery residency. Recruitment and match statistics show some variation, but the relevance of a shrinking applicant pool to these changes is unclear. Resident working conditions remain a difficult issue, and attrition rates continue to be significant. A substantial research agenda remains in graduate surgical education.

Attitude of Health Personnel↗
PubMed2002

Adjuvant effect of a Flt3 ligand (FL) gene-transduced xenogeneic cell line in a murine colon cancer model.

BACKGROUND: Flt3 Ligand (FL) has been shown to elicit antitumor responses induced by tumor antigen stimulation. Allogeneic and xenogeneic cell lines transduced with cytokine genes may be used to augment the antitumor efficacy of tumor antigens. OBJECTIVES: The objective was to evaluate the augmentation of tumor lysate-induced immunity by a more clinically applicable FL gene-transduced xenogeneic cell line in combination with interleukin-2 (IL-2) in a CC-36 murine colon cancer model. METHODS: Human 143B osteosarcoma tumor cells were transduced with full-length FL cDNA (143B-FL). Secretion of FL from 143B-FL was analyzed in vivo in normal BALB/c mice transplanted with 143B-FL, and expansion of dendritic cells (DC) was also analyzed in the same mice by flow cytometry. Eight-week-old, male BALB/c mice were used in a prophylactic vaccination protocol utilizing tumor lysate (CLy), 143B-FL, and soluble IL-2. Prophylactic group designations (n = 10/group) were as follows: ten million 143B-FL cells (alone, with tumor lysate, or with tumor lysate and IL-2), IL-2 with tumor lysate, IL-2 alone, or a no treatment control. The tumor lysate (200 microg of protein) and IL-2 (100,000 IU) injections were administered intraperitoneally. Mice were challenged subcutaneously with 10(3) CC-36 tumor cells. Tumor protection and tumor burden (TB), as mean tumor diameter, were determined. Peripheral blood lymphocytes (PBLs) from the 143B-FL + IL-2 + tumor lysate vaccinated group were analyzed for cytolytic activity in 4-h chromium release assays. In addition, plasma cytokine concentrations of interleukin-12 (IL-12) and interferon gamma (IFN-gamma) were assessed by ELISA. Student's t tests were used for all statistical comparisons. RESULTS: In vivo expression of FL was observed 24 h following the inoculation of 143B-FL, and a four fold increase in DCs was observed in the peripheral blood of these mice. Mice immunized with a combination of 143B-FL, tumor lysate and IL-2 showed statistically significant protection against tumor development (10%) for 100 days after tumor challenge; incidences in other groups ranged from 40 to 100% (P < 0.05). Moreover, this immunization protocol produced the lowest TB at 3- and 6-week time points (0, 1.6 mm) when compared to all other groups (TB between 7.2 and 15.9 mm) (P < 0.05). In addition, PBLs from vaccinated mice showed increased cytolytic activity against CC-36 target cells. This corresponded to increased levels of IL-12 and IFN-g in the plasma of mice following vaccination. CONCLUSIONS: These data suggest that FL gene-transduced xenogeneic tumor cells may augment the immunity induced by tumor antigens and systemic IL-2 through the activation of dendritic cells and T-cell-mediated mechanisms.

Adenocarcinoma↗
PubMed2002

Experimental melanoma vaccines.

There are several immunological implications for the feasibility of melanoma vaccines. Vaccines such as melanoma cell and cell-lysate preparations, chemically characterized and pure melanoma associated antigens (MAA), anti-idiotypic antibodies mimicking MAA, and vectors encoding the genes of MAA have been tested in early and advanced clinical trials. Some of these experimental vaccines have increased overall survival rate and increased disease-free interval rate in patients with melanoma. Some of these vaccines are currently being tested in randomized, controlled, phase III trials to confirm clinical efficacy, and it is possible that they will be used later in the standard care for melanoma.

Journal Article↗