Cancer Studies Active at the VA Long Beach Healthcare System

# 

# Thomas Ahlering, M.D.

> **#00400 Outcomes and Assessment of Prostate Cancer at the Long Beach
> VAMC.**

This study proposes to evaluate the \"outcomes\" of Prostate Specific
Antigen (PSA) and Transrectal Ultrasound (TRUS) guided prostate needle
biopsy (PNB) in the detection of prostate cancer progression. The stage,
grade, and age migration over the time period 1984-present are
evaluated, which will presumably have a positive effect on treatment
outcome. Data is obtained by a retrospective chart review as well as
from the LBVA on-line data retrieval system and the LB VAMC Tumor
Registry. Records of each patient are reviewed to determine the
patient's age and PSA at diagnosis, stage, grade, treatment modality,
and survival based on treatment. The general profile on all patients who
underwent TRUS/PNB is studied to review their complications.

> Identifying high/low risk prostate cancer patients is an important
> focus of prediction. They are investigating the outcomes of radical
> prostatectomy for men who average six or more years of follow-up. More
> than 40 % of these men have had prostate specific antigen (PSA)
> progression (defined by a rise of PSA \> 0.2 ng/ml) after surgery.
> Some Urologists have termed these men \"treatment failures\",
> believing that this PSA rise represents a recurrence of the cancer
> with ominous outcomes. Our preliminary results show that roughly half
> of these \'treatment failures\' have PSA doubling times of two years
> or more and thus can be safely followed without treatment for the
> first decade after surgery. The no-treatment group also benefits from
> a longer interval beyond surgery for PSA to become detectable, and
> have less aggressive cancer (Gleason score of 2). A manuscript
> detailing these findings has been submitted for review to the journals
> Prostate and Prostate Cancer. One archival paraffin block from each of
> 60 prostatectomies tested for biological markers of blood vessel
> formation was studied to create a predictive \'angiogenic index\' of
> prostate cancer. This work is currently being analyzed for
> publication.
>
> **Samar Azawi, M.D.**
>
> **#00043 Clinical Trial of Surgery Followed by Radiotherapy vs.
> Radiochemotherapy for Resectable High-Risk Squamous Cell Carcinoma of
> the Head & Neck.**
>
> The objective of this study is:

1.  Determine the efficacy of concurrent cisplatinum and radiotherapy
    following surgical resection of advanced squamous cell carcinoma of
    the head and neck region.

    i.  To test whether the use of concurrent chemoradiotherapy
        following surgery increases locoregional control rates.

    ii. To determine the patterns of first failure.

    iii. To determine whether the use of concurrent chemotherapy
         prolongs disease- free survival.

2.  To compare the toxicity of concurrent chemoradiotherapy vs.
    radiation alone in the postoperative setting. The patients with
    histologically proven primary squamous cell carcinoma of the oral
    cavity, oropharynx, hypopharynx, or larynx who underwent surgical
    resection and were found to have at least two histologically
    involved regional lymph nodes and/or extranodal disease and/or
    mucosal margins of resection that contain disease, without evidence
    of distant metastases, no previous chemotherapy or radiation therapy
    and good clinical renal function, will be randomized either to
    radiation therapy or to radiochemotherapy. Protocol treatment must
    begin within 8 weeks of first definitive tumor-related surgery.
    Patients are randomized to receive either radiotherapy alone versus
    radiochemotherapy. Radiation therapy is given, using standard
    radiation therapy and technique, to the tumor and regional
    lymphatics. Radiotherapy is started no later than 8 weeks following
    surgery. For Arm 2 (radiation and chemotherapy), chemotherapy is
    given on day 1, 22, and 43 with radiotherapy

> **#00523 A Phase III Comparison of Prophylactic Cranial Irradiation
> vs. Observation in Patients with Locally Advanced Non-Small Cell Lung
> Cancer.**
>
> The primary objective of this study is to determine whether
> prophylactic cranial irradiation (PCI) improves survival after
> effective locoregional/systemic therapy for patients with locally
> advanced non-small cell lung cancer (LA-NSCLC). Secondary objectives
> seek to determine: 1) The neuropsychologic impact of PCI, 2) The
> impact of PCI on QOL, and 3) The impact of PCI on the incidence of CNS
> mestastases. This study has two groups and each participant has an
> equal chance of being placed in either group. Group 1: Subjects in
> this group will receive radiation therapy to the brain once a day,
> Monday through Friday, for three weeks. Group 2: Subjects in this
> group will not receive radiation therapy to the brain. Their health
> and progress will be monitored. Patients with a histological diagnosis
> of non-small cell lung cancer who have completed locoregional/systemic
> chemotherapy, thoracic radiation therapy, and/or surgery will be
> randomized into the study to either Group 1 or Group 2
>
> **#00535 A Double-Blind Study of Nutritional Intervention for the
> Treatment of Cancer Cachexia Using the Juven Nutritional Supplement.**
>
> The purpose of this study is to investigate whether receiving a
> nutritional supplement will prevent weight loss, loss of lean tissue
> (muscle mass) and/or fatigue and how this affects the quality of life.
> The study will compare the effects (good and bad) of two nutritional
> supplements. The study involves the measurement of body weight and
> body mass over an eight-week treatment period. In addition, this study
> will compare methods of measuring changes in weight and muscle mass.
> About 468 people will take part in this study nationally,
> approximately 10 from this site.
>
> **#00565 A Phase III Randomized Study of High Dose 3D-CRT/IMRT vs.
> Standard Dose 3D-CRT/IMRT in Localized Prostate Cancer.**
>
> The primary objective of this study is to determine whether
> 3D-CRT/IMRT to 79.2 Gy in 44 fractions will lead to **improved overall
> survival** in patients treated for prostate cancer compared to that of
> patients treated with 3D-CRT/ IMRT to 70.2 Gy in 39 fractions. The
> secondary objectives are to:

1\. To determine freedom from PSA failure, disease-specific survival,
local progression, and distant metastases;

2.  To collect dose/volume data to allow tumor control and preservation
    of normal tissue in patients treated with radiation therapy for
    prostate cancer;

3.  To determine the incidence of grade 2 or greater GU and GI acute and
    late toxicity in patients treated with each of the regimens
    described above;

4.  To collect quality of life data.

5.  To collect diagnostic biopsy samples to determine the influence of
    histopathologic or tumor-specific cytogenetic changes on cancer
    control following radiation.

> **#00619 A Phase II Randomized Trial of Captopril in Patients Who Have
> Received Radiation Therapy + Chemotherapy for Stage II-IIIB Non-small
> Cell Lung Cancer (NCLC), Stage I Central NCLC or Limited-stage NCLC.**

This is a Phase II randomized trial involving patients with Stage
II-IIIB non-small cell lung cancer or Stage I central NSCLC or
limited-stage small-cell lung cancer to test the ability of Captopril to
alter the incidence of pulmonary damage at 12 months after radiation
treatment in a group of patients at significant risk for pulmonary
toxicity. The secondary objectives are:

1\. To investigate the pulmonary expression of MIP-la, TNF-a, IL-1, and
IL-6 at specific time intervals.

2.  To analyze whether the European Organization for Research and
    Treatment of

> Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the lung
> cancer module (QLQ-L13) scales are consistent in their measurement for
> pretherapy symptoms and ensuing changes after therapy for patients
> with primary lung cancer, including effects related to the addition of
> Captopril.

3.  To determine if Captopril\'s effect on pulmonary toxicity persists
    after completion of drug delivery.

#00611 Phase III Chemoprevention Trial of Selenium Supplementation in
Patients with Resected Stage I Non-Small Cell Lung Cancer.

> This is a double-blind, placebo-controlled, randomized study designed
> to evaluate the efficacy of selenium supplementation in reducing the
> incidence of second primary lung tumors in patients who have been
> treated for Stage I non-small cell lung cancer with complete surgical
> resection. The accrual goal for this phase III trial is 1960 eligible,
> consenting patients to enter the compliance run-in period. Subjects
> will be randomly assigned in a 2:1 ratio to receive either selenium
> yeast or placebo yeast respectively. After the initial 4-week
> treatment period, the patient will be evaluated for randomization by
> determining the number of tablets taken and the current disease
> status. Patients must consume at least 75% of tablets during the
> 4-week run-in period.
>
> Patients must be randomized within 3 to 6 weeks of start date of
> run-in period with nutritional supplement. Patients will then take
> selenium or placebo for up to four years and keep a log of missed
> doses. They will be contacted by telephone every six months and by
> mail in questionnaires until 2010.
>
> Eligible patients are those who have undergone complete resection of a
> histologically proven stage 1A (pT1N0) or stage 1B (pT2N0) non-small
> cell lung cancer who are currently free of disease. Eligible patients
> are between 6 and 36 months post surgical resection. Patients must not
> have received or be currently receiving chemotherapy or radiotherapy
> for lung cancer. Patients must be \> 18 years of age and have normal
> hepatic functions. Patients must have an ECOG performance status of
> 0-1. All laboratory values (including CBC) must be obtained within 8
> weeks prior to registration. Chest x-ray or CT scan \< 8 weeks prior
> to registration must show no sign of new or recurrent lung cancer.
> Patients currently taking mineral, herbal, phytochemical, or vitamin
> supplements at the time of entry must agree to continue on these
> supplements until the end of treatment. Patients not taking any of
> these supplements must agree not to start taking them during the
> study. Any supplement(s) containing \> 50 mcg of selenium are
> absolutely disallowed in this study.
>
> Patients with concurrent cancers or any prior cancer history within
> the past 5 years \[except localized non-melanoma skin cancer or
> synchronous lesions (lung + non-lung)\] or metastasis, even if
> respectable, are not eligible to participate. There can be no history
> of greater than one lung cancer primary at any time and patient must
> be free of disease at time of enrollment.

**Padmini R. Iyer, M.D.**

> **#00224 Early Stage Prostate Cancer Cohort.**
>
> The objective of this study is: (1) To establish a cohort of veterans
> with early stage prostate caner and collect baseline demographic,
> lifestyle habits, and medical history data to explore factors that
> predict transformation to clinically aggressive cancer (prostate
> cancer death or metastatic disease). (2) To establish a repository of
> frozen blood sample from same cohort of patients for future
> exploration of a wide variety of biochemical and genetic predictors of
> the risk of transformation to clinically aggressive cancer.

#00411 ZX101-301- A Phase III Randomized Controlled Study Comparing the
Survival of Patients with Unresectable Hepatocellular Carcinoma (HCC)
Treated with THYMITAQ to Patients Treated with Doxorubicin.

> This is a study to demonstrate that patients with unresectable HCC
> treated with THYMITAQ show an improvement in overall survival when
> compared to patients treated with doxorubicin. Specific Aims: (1) Time
> to progression and treatment failure (2) Overall response rate and
> response rate in patients who have received prior therapy vs. patients
> who have not received prior therapy 3) Rate of conversion from
> unresectable to resectable lesions (3) Probability of survival at 3,6,
> 9, and 12 months, (4) Drug safety, and (5) Clinical benefits.

#00493 A Randomized, Double Blind, Placebo Controlled, Trial of
Intravenous Zoledronic Acid (4 mg) to Prevent Osteoporosis in Men
Undergoing Androgen Deprivation Therapy in the VA Population.

> The primary objective of this study is to compare the effect of
> zoledronic acid and placebo when administered every three months (four
> treatments in one year), on bone loss associated with Androgen
> Deprivation Therapy (defined as LHRH agonist with or without another
> antiandrogen agent or orchiectomy) in men with stage M0 prostate
> carcinoma. A secondary objective is to compare the effect of
> zoledronic acid and placebo on the percent change in Bone Mineral
> Density (BMD) of the total hip (to include sub-regional analysis of
> the femoral neck, trochanteric region, and Ward's triangle) following
> one year of therapy. This study is a double-blind, multicenter,
> randomized, placebo controlled study of one year intravenous
> zoledronic acid 4 mg vs. placebo on the bone loss associated with ADT
> in men with non-metastatic prostate cancer. All subjects will also
> receive calcium/vitamin D supplementation and counseling about
> lifestyle modifications to optimize bone health. At randomization,
> patients will be stratified in three groups by the duration of ADT
> (less than 1 year, 1-3 years, or more than 3 years of ADT) and
> randomly assigned to either zoledronic acid or placebo. Each of the
> three groups of patients will comprise 80 men with 40 men assigned to
> each treatment arm for a total of 240 men.
>
> **#00599 The Use of Zoledronic Acid in Men on with Pre-existing
> Osteoporosis receiving Androgen Deprivation Therapy for Prostate
> Cancer.**
>
> This study is an open-label, multicenter study of 1 year zoledronic
> acid treatment on bone loss associated with ADT in men with
> non-metastatic prostate cancer with pre-existing osteoporosis to
> evaluate the effect of zoledronic acid on bone health for men on ADT
> (LHRH agonist with or without an anti-androgen agent or orchiectomy)
> for stage M0 prostate cancer who have severe osteopenia or
> osteoporosis The secondary objective is to evaluate the percent change
> in BMD of the lumbar spine (L2-L4) by DEXA scan comparing each
> patient's baseline study to their DEXA scans at 6 and 12 months. All
> subjects will also receive calcium/vitamin D supplementation and
> counseling about lifestyle modifications to optimize bone health.

The study population in this study consists of patients with stage M0
CAP having pre-existing severe osteopenia or osteoporosis in the lumbar
spine and/or the total hip as documented by DEXA scan who otherwise meet
the entry criteria for MIRB 493, a double blind study of zoledronic acid
vs. placebo for stage M0 CAP patients in the VA healthcare system. Other
patients with known pre-existing osteoporosis will be screened directly
and enrolled if they meet all entry criteria. The primary endpoint will
be BMD as estimated by DEXA scan at 6 and 12 months compared to baseline
for each patient.

> To be eligible, patients just starting ADT must have stage M0 prostate
> carcinoma (PSA \<10 or no radiographically demonstrable bony
> metastases). Patients already on ADT must have been M0 at initiation
> of ADT and have maintained a stable low PSA (\<2) on continuous ADT
> since that time. Eligible patients will receive the study drug
> administered intravenously over 15 minutes once every three months for
> four treatments. Participating patients will have safety assessments
> including physical exam at each study visit. A DEXA scan will be done
> at baseline and at 6 and 12 months after start of study treatment to
> measure BMD.

**Martin R. Jadus, Ph.D.**

> **#00304 Improving an mM-CSF Tumor Vaccine for Established
> Intracranial Gliomas.**
>
> In this study, the investigators are surgically implanting various T9
> glioma cells (viral vector, mM-CSF transduced clones, or parental
> unmodified cells) into rat brains while under general anesthesia.
> After the tumor is established, we are immunizing the rat
> subcutaneously with the mM-CSF transduced cells or intraperitoneally
> with anti-angiogenic drugs, which target the endothelial cells for the
> tumor. Tumor growth is then monitored by watching rats for signs of
> brain cancer, being moribund, unable to move, etc. It is essential
> that an assessment be made whether the drugs have sufficiently
> affected the endothelial cells within the tumor.
>
> **#00416 Can altM-CSF Explain the Beneficial Tumor Vaccinating Effect
> of mM-CSF?**
>
> Tumor cells transduced with the membrane form of macrophage colony
> stimulating factor (mM-CSF) are killed by macrophages, which results
> in systemic tumor immunity in vivo. The main hypothesis of this study
> is that a cytotoxic T lymphocyte (CTL)-mediated immune response is
> stimulated by the alternative spliced form of macrophage colony
> stimulating factor (altM-CSF). AltM-CSF is a naturally occurring
> variant peptide derived from M-CSF mRNA that is completely different
> from the M-CSF cytokine. Thus, the mechanism whereby tumor immunity
> has been generated with mM-CSF transduced tumor cells may be partly
> explained by immunity towards altM-CSF.
>
> **M. Mazen Jamal, M.D.**
>
> **#00590 A Phase 3, Multicenter, Single-Blind, Randomized Study of
> XL119 Versus 5-Fluorouracil (5-FU) plus Leucovorin (LV) in Subjects
> with Advanced Biliary Tumors not Amenable to Conventional Surgery.**
>
> The primary objective of this study is to compare survival duration
> for XL119- and 5-FU/LV-treated patients. Secondary objectives are to
> determine time to progressive disease for XL119- and 5-FU/LV-treated
> subjects, to evaluate the clinical benefit, and to assess the safety
> profile of XL119.
>
> Patients with biliary or gallbladder cancer not amenable to surgery
> who meet the following inclusion criteria: Advanced histologically
> confirmed biliary cancer that is not amenable to conventional surgical
> approach; life expectancy at least 12 weeks; Eastern Cooperative
> Oncology Group (ECOG) performance status score \<3; and at least 18
> years of age. Exclusion criteria are: prior chemotherapy, unstable
> angina, central nervous system metastases, uncontrolled diabetes
> mellitus, and uncontrolled seizure disorder
>
> Dose and mode of administration: XL119 will be administered as a
> 1-hour infusion by a central venous access device at a daily dose of
> 140mg/m^2^/day on days 1 through 5 of a 28-day cycle. Subjects may
> receive up to 12 cycles of treatment (approximately 12 months of
> treatment for a total of up to 60 infusions). If after 12 cycles of
> treatment, in the opinion of the investigator, the subject has not
> progressed and should continue to receive treatment with XL119, the
> subject my be enrolled into an open-label maintenance study, which
> will be conducted under a separate protocol.
>
> Inpatients, outpatients, and non-VA subjects will be recruited.

## Jayashri Kidao, M.D.

#00455 A Phase III Randomized, Double-Blind, Placebo-controlled Clinical
Trial of the Combination of DFMO and Sulindac to Decrease the Rate of
Recurrence of Adenomatous Polyps in the Colon.

> The proposed study is a randomized placebo-controlled double-blind
> Phase III trial of the combination of DFMO plus Sulindac vs. double
> placebos in patients with prior adenomas. The trial will utilize a
> stratified (for site) and randomized design, an 4 week run-in period
> with double-placebo for all qualifying subjects, and an
> intent-to-treat paradigm, and analysis. All patients will have had a
> qualifying colonoscopy within 6 months of study entry by a validated
> study endoscopist and 3 years after randomization. Sigmoidoscopy with
> 8 mucosal biopsies 10-15cm above the anal verge will be done
> pre-randomization and after 36 months of therapy. Biopsies will be
> snap-frozen to --800 and analyzed for polyamine content and PGE2
> levels.. Patients will be serially monitored for side effects and a
> baseline and 36-month pure tone audiogram routinely obtained; if
> clinical hearing changes occur during the 36 month study period an
> additional audiogram will also be done. Our study will also monitor
> various biochemical tests, urine analysis and pill counts to document
> adherence and safety. At each colonoscopy, the endoscopist will record
> the size and location of all mucosal lesions. All adenomas will be
> removed and examined histologically and measured at the clinical site
> and by the study pathologist. Polyps will be classified as adenomas or
> non-adenomas (hyperplastic polyps or lymphoid follicles).

#00016 Prospective Evaluation of Risk Factors for Large Colonic Adenomas
in Asymptomatic Subjects.

> This is a study to determine if specific historical factors,
> environmental factors or biological markers can identify candidates
> for targeted screening program for colorectal neoplasia. In Phase I,
> 3196 asymptomatic patients (age 50 to 75 years) were enrolled, and
> completed screening colonoscopy. The prevalence, size and location of
> neoplastic lesions was determined. The primary study aim was to assess
> risk factors for advanced neoplasia. In Phase II, selected patients
> were entered into a 5-year follow-up program. The goals of the
> follow-up phase were to determine the 5-year risk of developing
> recurrent neoplasia in patients with neoplasia at baseline, and the
> risk of developing new neoplasia in patients who were adenoma-free at
> baseline. Phase II was completed in March 2002. The Phase III
> objectives are: (1) To define 10-year colon cancer incidence rates in
> patients who have had screening with colonoscopy and compare these
> rates with age- and gender-adjusted expected rates; (2) To perform
> colonoscopy at 10 years in a cohort of patients who were age 50-64 at
> baseline, and had no neoplasia; (3) To determine the risk of advanced
> neoplasia and colorectal cancer at 10 years in patients with advanced
> neoplasia at baseline; and (4) To identify risk factors for incidence
> of advanced neoplasia and cancer during the follow-up period.

## Christine LaMarre, M.D.

> **#00206 Bowman-Birk Inhibitor and Oral Leukoplakia Phase IIb Trial.**
>
> The purpose of this study is to determine whether Bowman-Birk
> Inhibitor Concentrate (BBIC), a protease inhibitor extracted from
> soybeans, can reduce intermediate marker endpoints (IME) in buccal
> mucosal cells in patients with oral leukoplakia. The overall objective
> of this study is to determine whether chemoprevention can prevent
> cancer in humans. Oral leukoplakia (OL), an easily assessable,
> clinically identifiable precursor of head and neck cancer, represents
> an excellent model system for the study of chemoprevention. The
> specific aims for the Phase IIb study are to conduct a
> placebo-controlled, double-blind and randomized 6-month cancer control
> chemoprevention trial of BBIC in patients with OL. The essential
> features include: (1) To determine the clinical and histologic
> response rate of OL to BBIC; (2) To measure serially the effect of
> BBIC on IME levels; (3) To correlate the clinical and histologic
> responses of OL lesions and the levels of protease activity (PA),
> erb-B2 (neu), RAR-beta, bcl-2, mutant p53 expression, and serum levels
> of neu; and (4) To determine the individual and group side effects of
> BBIC.
>
> This study will test the effects of 600 CI units of BBIC on IME for
> the development of oral cancer in patients at risk for oral cancer.
> These endpoints will include the visual and histological status of OL,
> and selected biochemical markers. Patients will receive either BBIC or
> flour placebo for six months, and if they demonstrate partial or
> complete response, will be continued on either study drug or placebo
> for an additional twelve months. Periodically during the study, blood,
> urine and buccal mucosa specimens will be obtained and symptoms will
> be evaluated to monitor for any evidence of drug toxicity. Research
> results will be derived mainly from measurement of drug treatment
> effect on lesion size and tissue using small amounts of blood, buccal
> mucosa specimen, and biopsies of the oral cavity. All study procedures
> will be conducted in compliance with the Study Protocol, NCI Good
> Clinical Practice guidelines, and any applicable regulatory
> requirements.

## Ellis R. Levin, M.D.

> **#00026 Isolation and Vascular Function of the Membrane Estrogen
> Receptor**
>
> This animal study seeks to isolate and characterize the cell membrane
> estrogen receptor from blood vessel cells. The research design is a
> cell-based and molecular biology approach, including determining
> signal transduction to the biology of estrogen action. Isolation of
> the protein from transfected CHO cells or native cells is
> accomplished, and modulation of the signal pathways activated by
> estrogen is determined. Recent findings have demonstrated that the
> plasma membrane and nuclear receptors are identical. The membrane
> receptor resides in the caveolae where it transduces signaling to
> downstream kinases, important for survival and proliferation of both
> vascular and breast cancer cells. The membrane receptor signals to the
> biology of estrogen action and is a therapeutic target to prevent
> breast cancer development or to stimulate new blood vessels.
>
> **#00543 Plasma Membrane Estrogen Receptor Transgenic Mouse.**
>
> The primary objective of this study is to raise and characterize
> transgenic mice that express estrogen receptors only at the plasma
> membrane or in the nucleus. It is hoped that understanding the exact
> location of estrogen actions can lead to new therapeutic treatments.
>
> **#00428 Non-genomic Actions of Estrogen in Breast Cancer**
>
> Estrogens have many different effects, and this study will use breast
> cancer cells to study the mechanisms whereby estrogen promotes the
> survival and proliferation of breast cancer. The study will
> investigate if novel, non-genomic actions of estrogen acting at the
> plasma membrane are responsible for this effect. Breast cells may have
> a protein that promotes apoptosis, but estrogen may affect this gene
> adversely. This study will further investigate the mechanisms of
> estrogen.

## Edgar M. Moran, M.D.

> **#00496 Genetic and Environmental Factors and the Risk of Male Breast
> Cancer**

This study is designed to investigate the association between male
breast cancer risk and genetic and environmental factors. A
hospital-based retrospective chart review will be utilized. Male breast
cancer cases and controls matched on age +/- 5 years and ethnicity will
be identified by means of the VA hospital database. No personal
identifiers will be used. The data abstracted from medical records will
use only the last 4 digits of the social security number. The VA patient
database is password protected. Study records and charts will be
securely locked in cabinets exclusively at the VA. Information gained
from this study may improve our knowledge of breast cancer etiology and
prevention through a better understanding of the risk factors.

## Timothy R. Morgan, M.D.

> **#00625 A National Registry of Patients with Hepatocellular
> Carcinoma.**
>
> This study seeks: (1) To evaluate the etiologic factors associated
> with hepatocellular carcinoma in different ethnic groups and in
> different parts of the United States; (2) To survey stage and
> potential treatability of patients with hepatocellular carcinoma
> referred to the Long beach VA Healthcare System; (3) To establish a
> serum repository from patients with HCC for future studies aimed at
> understanding the pathogenesis of chronic liver disease and HCC and to
> develop better diagnostic tests for HCC. The national part involves
> similar data to be collected from other liver centers around the
> country and will be entered into a computerized database managed at
> St. Louis University, St. Louis, MO.

## H. Terry Wepsic, M.D.

> **#00545 Membrane MCSF Transduced U251 Glioma Stimulates Human
> Immunity in vivo.**
>
> This animal study seeks to determine whether human glioblastoma cells
> , which are transduced with the gene for the membrane form of
> macrophage colony stimulating factor (mM-SCF), can induce immune
> responses by HLA-A2 matched human peripheral blood mononuclear cells
> that have been innoculated into immunodeficient SCID/bg/xid mice. The
> objectives of this study are threefold: (1) Identify if the mM-CSF
> tumor cells are dying of a novel programmed form of death called
> paraptosis and identify the genes responsible for this phenomenon; 2)
> Demonstrate that the antigen presenting function of the antigen
> presenting cells, such as the dendritic cells, have increased
> antigenic uptake, antigenic presentation, and cell signaling pathways
> and; (3) Identify the T cell subsets that have become activated as a
> result of antigen presenting function by mM-CSF-transduced U251 cells.

**David H. Wong, M.D., Pharm.D.**

> **#00620 Pathological Staging Data for Colon Cancer Patients Entered
> in CSP #345, Choice of Anesthesia: General vs. Epidural.**
>
> This is a follow-up to the original VA Cooperative Study, conducted
> between 1990-1992. The primary objective of this protocol is to
> collect pathological cancer staging data (TNM and, if available Dukes'
> staging) on 247 colon cancer patients who were randomized to
> unsupplemented general anesthesia (USGA) or epidural-supplemented
> general anesthesia (ESGA) in CSP 345. This data will be collected from
> the tumor registries of the 15 VA medical centers that participated in
> this cooperative study. The objective of this study is to collect the
> pathological staging data of the original patients.