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Biomedical subjects

C G Collins

Publications and source records attributed to C G Collins.

13 recordsLinked to original sources
PubMed2006

Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors.

Gene therapy-induced expression of immunostimulatory molecules at tumor cell level may evoke antitumor immune mechanisms by recruiting and enhancing viability of antigen-processing cells and specific tumoricidal lymphocytes. The antitumor efficacy of a plasmid, coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) and the B7-1 costimulatory immune molecule, delivered into growing solid tumors by electroporation was investigated. Murine fibrosarcomas (JBS) growing in Balb/C mice (<or=100 mm3) were transfected with GM-CSF/B7-1-expressing plasmid. Complete tumor regression occurred in greater than 60% of treated animals. This response was systemic, durable and tumor specific, with all responding animals resistant to repeat tumor challenge. Using a liver metastatic model, effective cure of distal metastases was achieved following treatment of the primary subcutaneous tumor. This treatment strategy could be applicable in the clinical setting for effective elimination of both primary tumors and associated metastatic disease.

Animals↗
PubMed2006

Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease.

Many patients with various types of cancers have already by the time of presentation, micrometastases in their tissues and are left after treatment in a minimal residual disease state [Am J Gastroenterol 95(12), 2000]. To prevent tumour recurrence these patients require a systemic based therapy, but current modalities are limited by toxicity or lack of efficacy. We have previously reported that immune reactivity to the primary tumour is an important regulator of micrometastases and determinant of prognosis. This suggests that recruitment of specific anti-tumour mechanisms within the primary tumour could be used advantageously for tumour control as either primary or neo-adjuvant treatments. Recently, we have focused on methods of stimulating immune eradication of solid tumours and minimal residual disease using gene therapy approaches. Gene therapy is now a realistic prospect and a number of delivery approaches have been explored, including the use of viral and non-viral vectors. Non-viral vectors have received significant attention since, in spite of their relative delivery inefficiency, they may be safer and have greater potential for delivery of larger genetic units. By in vivo electroporation of the primary tumour with plasmid expressing GM-CSF and B7-1, we aim to stimulate immune eradication of the treated tumour and associated metastases. In this symposium report, we describe an effective gene based approach for cancer immunotherapy by inducing cytokine and immune co-stimulatory molecule expression by the growing cells of the primary tumour using a plasmid electroporation gene delivery strategy. We discuss the potential for enhancement of this therapy by its application as a neoadjuvant to surgical excision and by its use in combination with suppressor T cell depletion.

B7-1 Antigen↗
PubMed2005

Paraesophageal lymph node metastasis from prostatic adenocarcinoma in a patient with esophageal squamous carcinoma.

SUMMARY. Esophageal squamous carcinomas induce regional immune suppression in the domain of the tumor while the global immune system remains intact. We report a patient with a squamous esophageal carcinoma, who was discovered at esophagectomy to have paraesophageal lymph node metastases from a prostatic adenocarcinoma. No other sites of metastatic disease were identified. This supports the concept that regional immune suppression by esophageal squamous cancers facilitates growth of metastases in the local lymph nodes.

Adenocarcinoma↗
PubMed2003

Oral immune tolerance to tumor specific antigens may confer growth advantage to esophageal and gastric cancers.

Oral administration of antigens induces antigen-specific systemic immune tolerance (Oral Tolerance). We postulate that the poorer prognosis of foregut cancers might, in part be explained by the systemic immune tolerizing effect of tumor specific antigens shed into and processed by the gut immune system thus conferring a growth advantage specific to individual cancers. Immunocompetent Balb/c mice were fed by gavage, either tumor tissue (JBS/CarB) in phosphate buffered saline (PBS) or PBS alone, daily for 14 days. On day 15 either subcutaneous tumors were induced or animals were immunized with cells in adjuvant. JBS tumors appeared earlier and grew faster in the JBS tumor fed mice than in either the PBS (P = 0.025) or CarB (P = 0.168) fed animals. The delayed type hypersensitivity response in tolerized mice was significantly abrogated (P < 0.01) compared to controls. These experiments demonstrate antigen specific oral immune tolerance for tumors, which is reflected in a faster growth rate and impaired delayed type hypersensitivity response. Similar mechanisms may be operational in human esophagogastric malignancy and may in part explain their poorer outcome.

Animals↗
PubMedDate not supplied

Adult intussusception--need for en-bloc resection.

BACKGROUND: Adult intussusception is an uncommon surgical presentation AIMS: We report a case of adult intussusception, review the literature and discuss the optimal management. METHODS: We describe a woman who presented with severe abdominal pain and a large supra-umbilical mass. Ileocolic intussception was confirmed on CT, and a laparotomy and en-bloc resection were carried out. Postoperatively she made an uneventful recovery. CONCLUSION: Adult intussusception is a rare clinical presentation. En-bloc resection should be the surgical treatment of choice in the majority of cases due to the high percentage of malignant lead points.

Adenoma↗