Angiogenesis and growth of murine colon carcinoma are dependent on infiltrating leukocytes.

We determined whether the angiogenesis and growth of murine colon carcinomas growing in the wall of the cecum is dependent on infiltrating leukocytes. Syngeneic BALB/c or SCID mice were treated with a myelosuppressive, maximally tolerated dose of doxorubicin. Parental or multidrug resistant CT-26 colon carcinoma cells were implanted into the cecal wall 3 days after the second intravenous injection of doxorubicin. Control mice developed large, well-vascularized tumors, whereas doxorubicin-pretreated mice did not. Intravenous injection of spleen cells from normal BALB/c or SCID mice one day prior to tumor cell implantation reversed the decreased vascularity and tumorigenicity. The production of proangiogenic molecules and microvessel density in tumors directly correlated with the number of infiltrating leukocytes, suggesting that tumor-infiltrating leukocytes are essential to angiogenesis of murine colon carcinomas.

Characterisation of the vasculature within a murine adenocarcinoma growing in different sites to evaluate the potential of vascular therapies.

Numerous vaso-active agents can affect vasculature in experimental solid tumours growing subcutaneously (s.c.), but these models are unlikely to reflect the vasculature of metastatic disease in man. The present study describes a murine orthotopic colon tumour which metastasises to the liver. Morphology and vascular pattern of caecal tumours is similar to s.c. tumours. Vascular occlusion caused by intravenous (i.v.) noradrenaline (NA) (160 micrograms kg-1) and hydralazine (HDZ) (10 mgkg-1) was 32% and 59% respectively for the caecal tumours compared with 35% and 78% for s.c. tumours. Significant morphological differences were seen between liver metastases and systemic deposits produced by i.v. inoculation of tumour cells. Liver metastases following orthotopic transplantation contained functional vasculature but no significant occlusion was seen with NA or HDZ. The vascular development and morphological appearance of secondary disease resulting from orthotopic implantation suggests that this would be a useful model for the study of agents that act either by vascular or anti-angiogenic mechanism.

The effects of pentoxifylline on the relative perfusion of tumours growing in three sites in the mouse.

The haemorheological agent pentoxifylline (PTX) has been shown to improve the relative perfusion and oxygenation of subcutaneous tumours in the mouse. In order to establish whether this effect is dependent on the site of tumour growth, we have looked at changes in the distribution of the cardiac output (COD) to the murine NT carcinoma grown either intradermally (i.d.), intramuscularly (i.m.), on the wall of the caecum, or in all three sites, following i.p. administration of 50 mg kg-1 PTX. In animals bearing a single tumour, PTX treatment significantly increases the COD to tumours located in the caecum, but has no significant effect on the COD to those located in the i.d. or i.m. sites. If all three tumours are present in a single animal, the COD to all three tumours is significantly enhanced by PTX. This appears to reflect the presence of the caecum tumour and does not appear to relate to changes in tumour size or to the haematocrit (HCT) of the blood. We propose that this site dependency implies that a significant increase in blood viscosity only occurs in animals with tumours located in specific sites. Therefore, the potential radiosensitising capability of PTX is highly dependent on tumour location.

Canine intestinal carcinoids.

Intestinal carcinoids were diagnosed in three aged dogs. Two of the neoplasms occurred in the rectum and one at the cecocolic junction. Judged by histologic criteria, all three carcinoids were considered to be malignant. Amyloid was present in both rectal tumors. In each tumor the diagnosis was confirmed by the finding of electron-dense intracytoplasmic secretory granules in the neoplastic cells.

Jejunoileal arteriovenous malformation: localization for resection by segmental bowel staining techniques.

Arteriovenous malformations, submucosal vascular lakes, of the jejunum and ileum which cause chronic gastrointestinal bleeding and anemia are easily identified before operation by selective arteriography but difficult at operation owing to lack of physical signs. This report is concerned with a patient who had such a lesion located in the proximal jejunum. The involved segment was easily identified at operation by injection of Indigo Carmine solution during operation into the involved jejunal artery subselectively catheterized immediately prior to operation. The duration of jejunal staining before resection was 45 minutes in this case and varied from 35 to 55 minutes in five other patients who had right colectomy for carcinoma, providing the opportunity to inject accurately in a conveniently located radiology suite before operation. Safe, convenient, longer periods of staining which could be performed at the time of original diagnosis were demonstrated in dog experiments using "biologic" colloidal carbon in which the bowel segment was well stained at the time of sacrifice five days after injection. There were no gross or microscopic signs of injury to bowel.