Biomedical subjects

Emina H Huang

Publications and source records attributed to Emina H Huang.

6 recordsLinked to original sources

PubMed2006

Induction of inflammatory bowel disease accelerates adenoma formation in Min +/- mice.

BACKGROUND: The accelerated incidence of colorectal carcinoma in individuals with inflammatory bowel disease suggests that cellular perturbation triggered by chronic inflammation is linked to the development of dysplasia and neoplastic transformation. To test the mechanistic links between these processes, we employed the following murine strains: (1) multiple intestinal neoplasia (Min) +/- mice, bearing a mutation in the adenomatous polyposis coli (APC) gene; (2) mice deficient in interleukin 10 (IL-10), which normally develop enterocolitis; and (3) Min +/-/IL-10 null mice, first developed in our laboratory. METHODS: Mice with either parental strain or the cross were sacrificed at time points ranging from 10 to 30 weeks of age. The small bowel and colon of 170 IL-10 null mice, 31 Min +/- mice, and 120 Min +/-/IL-10 null mice were examined microscopically. RESULTS: The number of flat adenomas was increased in the colons of the Min +/-/IL-10-/- mice, compared with the Min +/- mice (P = .0005). Neither colitis-type dysplasia nor carcinoma was increased in the Min +/-/IL-10 -/-, compared with the IL-10 null mice (P = .18). Mice deficient in IL-10 developed colitic-type dysplasia (P = .0001) or carcinoma (P = .0001) correlated with increasing inflammation. CONCLUSIONS: Breeding the Min +/- genotype into the IL-10 -/- background increased the incidence of colonic adenomas. Our studies demonstrate that acceleration of dysplasia and progression to invasion were associated with the degree of the inflammatory response in mice deficient in IL-10. These findings provide a novel system to dissect the pathways by which inflammatory mechanisms accelerate adenoma formation.

Adenoma↗

PubMed2006

Perioperative immunomodulation with Flt3 kinase ligand or a whole tumor cell vaccine is associated with a reduction in lung metastasis formation after laparotomy in mice.

INTRODUCTION: Laparotomy has been associated with temporary postoperative immunosuppression and accelerated tumor growth in experimental models. In a previous murine study, a whole cell vaccine plus the adjuvant monophosphoryl-lipid A was shown to be effective in decreasing the number of lung metastases that develop after laparotomy. This study was conducted to assess the impact of the adjuvant fetal liver tyrosine kinase 3 (Flt3) ligand on perioperative tumor growth when used alone or with a tumor cell vaccine. METHODS: An intravenous tumor cell injection lung metastases model was used. Sixty female A/J mice were divided into six equal groups designated (1) anesthesia control (AC), (2) AC with Flt3 ligand (ACFlt3), (3) sham laparotomy (OP), (4) OP with Flt3 ligand (OPFlt3), (5) OP with vaccine (OPVac), and (6) OP with Flt3 ligand and vaccine (OPFlt3Vac). Groups 2, 4, and 6 received daily intraperitoneal injections of Flt3 ligand (10 microg/dose with carrier) for 5 days before and 5 days after surgery. Groups 1 and 3 received similar injections of saline on the same schedule. Groups 5 and 6 were vaccinated with irradiated whole Ta3Ha tumor cells intraperitoneally three times before and twice after surgery. Immediately after surgery, all mice were injected with 10(5) Ta3Ha tumor cells via a tail vein. After 14 days, the mice were sacrificed and their lungs and tracheas were excised en bloc. Specimens were stained and counterstained with India ink and Fekete solution, and surface metastases were counted by a blinded observer. Differences between study groups were determined by analysis of variance. The peritumoral inflammatory cell infiltrate of some Flt3 and control specimens was also assessed. RESULTS: Regarding laparotomy, Flt3 ligand (mean, 1.22 metastases), whole cell vaccine (1.12 metastases), and the combination of these two agents (0.1 metastases) were each effective in significantly decreasing the number of surface lung metastases compared with surgery alone (9.88 metastases, P < .05 for all comparisons). There were no differences between the various treatment groups in regards to number of metastases. Only the combination of Flt3 and the vaccine significantly lowered the incidence of tumors (number of mice with > or =1 tumors). Histologic analysis revealed that the Flt3-treated mice demonstrated increased numbers of antigen-presenting cells surrounding the tumors compared with controls. CONCLUSIONS: Perioperative treatment with either Flt3 ligand or a whole cell tumor vaccine significantly reduced the number of lung metastases after laparotomy. The combination of the Flt3 ligand and the vaccine also decreased the incidence of metastases and was the most effective treatment. Further studies regarding perioperative immune modulation in the setting of cancer appear warranted.

Adenocarcinoma↗

PubMed2004

B cell response to tumor antigens is associated with depletion of B progenitors in murine colocarcinoma.

BACKGROUND: B cells that produce antibodies to autologous tumor antigens have been found in patients with colon cancer; the significance of this phenomenon remains unknown. Normally, the elimination of autoreactive B cells occurs in the bone marrow during their maturation. We studied the production of antibodies to syngeneic tumor antigens and the maturation of bone marrow B cells in experimental colocarcinoma model. METHODS: BALB/c mice and syngeneic CT26 colon cancer cell line were used. Reactivity of serum antibodies was tested in Western blot analysis and flow cytometry against CT26 antigens. The number of bone marrow B lineage cells was evaluated with specific antibodies and flow cytometry analysis. RESULTS: A significant decrease in the number of B cell precursors occurred in tumor-bearing mice; it normalized 3 weeks after the removal of CT26 tumors. The number of mature B cells was normal. Serum antibodies from tumor-bearing mice recognized intracellular and not surface antigens of CT26 cells. CONCLUSION: Experimental colon cancer induces B cell response to intracellular, but not surface, tumor cell antigens and restricts the B cell repertoire by depleting their precursors.

Adenocarcinoma↗

PubMed2002

Plasma from patients undergoing major open surgery stimulates in vitro tumor growth: Lower insulin-like growth factor binding protein 3 levels may, in part, account for this change.

BACKGROUND: Plasma from laparotomized mice has been shown to stimulate in vitro tumor growth when compared to results with preoperative plasma. This study assessed the effect of plasma from patients who underwent major open (OS) or laparoscopic surgery (LS) on in vitro tumor cell growth. METHODS: Eighty-four patients undergoing major abdominal surgery were studied (45 OS, 39 LS). Peripheral blood was collected preoperatively (PreOP) and on days 1 (POD1) and 3 (POD3) after operation. HT29 human colon cancer cells were plated with samples of the plasma. Proliferation was assessed by cell counts and the bromodeoxyuridine incorporation assay. Insulin-like growth factor binding protein 3 was detected in plasma by Western blot analysis. RESULTS: Increased mitogenic activity was noted in POD1 OS plasma when compared to PreOP OS plasma results (P <.005). This increase correlated with the length of incision (r = 0.58, P <.01). No differences were noted when the PreOP LS and POD1 LS results were compared or for any of the POD3 versus PreOP comparisons. CONCLUSIONS: Major OS is associated with alterations in plasma composition that promote HT29 tumor cell proliferation in vitro. As shown, this effect was due, at least in part, to surgery-related depletion of insulin-like growth factor binding protein 3 in peripheral blood.

Antibodies↗

PubMed2002

CEA-based vaccines.

Carcinoembryonic antigen (CEA), the first tumor-associated antigen to be described, was cloned in 1987 and is expressed on nearly 50% of all human tumors. The identification of T-cell specific epitopes within the coding region of the CEA protein has led to the development of various vaccine strategies that target CEA and CEA-expressing tumors. These vaccines have shown evidence of therapeutic effectiveness in animal models and are being evaluated in early phase clinical trials. Although trials are not designed to elucidate clinical responses, they have provided important information about the ability of individual vaccines to induce CEA-specific immune responses through the use of newer in vitro monitoring assays. Continued clinical testing in patients with less advanced disease and the administration of vaccines in combination with other standard therapy will help define the role of CEA-based vaccines in the treatment and prevention of human cancer.

Animals↗

PubMedDate not supplied

Safety and reliability of tattooing colorectal neoplasms prior to laparoscopic resection.

Accurate tumor localization is critical to performing minimally invasive colorectal resection. This study reviews the safety and reliability of tattooing colorectal neoplasms prior to laparoscopic resection. We retrospectively reviewed 50 consecutive patients with colorectal neoplasms who underwent endoscopic tattooing prior to laparoscopic resection. Data were obtained from medical charts, endoscopy records, and pathology reports. No complications related to endoscopy or tattooing were incurred. Five neoplasms (10%) were in the ascending colon, five (10%) were in the transverse colon, eight (16%) were in the descending colon, 23 (46%) were in the sigmoid colon, and nine (18%) were in the rectum. Tattoos were visualized intraoperatively and accurately localized the neoplasm in 44 patients (88%). Six patients (12%) did not have tattoos visualized laparoscopically and required intraoperative localization. On average, the pathology specimens in this series had a 15 cm proximal margin, a 12 cm distal margin, and 15 lymph nodes. In the context of laparoscopic colorectal resection, preoperative endoscopic tattooing is a safe and reliable method of tumor localization in most cases. Localizing colon and proximal rectal lesions with tattoos may be preferable to other localization techniques including intraoperative endoscopy.

Adenoma↗