In vivo therapeutic effects of interleukin-12 against highly metastatic residual lymphoma.

Despite considerable advancement in anticancer therapy, minimal residual disease (MRD) is still a major problem in the clinical management of cancer, including lymphoma. In this report, we have studied the antitumor effects of interleukin-12 (IL-12) against an aggressive liver metastatic murine RAW117-H10 lymphoma. Our results using three different doses of IL-12 (0.175, 0.35 and 0.7 micrograms/mouse) showed that a 0.35 micrograms dose is the most efficacious against lymphoma grown in intact mice. Furthermore, we have evaluated the therapeutic effects of IL-12 against residual lymphoma in a transplantation setting. BALB/c mice were treated with high-dose therapy (HDT) and transplanted with syngeneic bone marrow cells added with a known number of RAW117-H10 lymphoma cells to mimic the clinical situation of MRD. The mice were then treated with IL-12 (0.25 micrograms/mouse/day) alone or IL-12 plus activated cytotoxic effector cells. Our results showed that IL-12 had a significant (P < 0.05) antitumor therapeutic effect against liver metastatic lymphoma grown in intact mice as well as in lymphoma-bearing mice treated with HDT followed by stem cell transplantation as determined by survival period. The therapeutic effect of IL-12 was also demonstrated by a very significant decrease (P < 0.05) in the tumor burden in livers from the IL-12-treated mice. Mice that were treated with IL-12 following HDT and hematopoietic stem cell transplantation had a significant decrease in circulating white blood cells (P < 0.05), a significant increase in spleen weight and cellularity (P < 0.05), and hematopoietic progenitor cells (P < 0.05), a significant increase in the number of splenocytes expressing IL-2 alpha-chain receptor (P < 0.05), and an increase in the frequency of natural killer cells in their spleens. These studies suggest that cytokines such as IL-12 may have the potential to mediate antitumor effects against residual lymphoma without compromising lymphohematopoietic recovery.

The fine structure of experimentally induced connective tissue complexes in the human.

The growth, development and cellular activity of fibrocollagenous tissue complexes induced by the implantation of specially structured wire mesh cylinders in 22 human male volunteers were studied during the time course of fibroplasia utilizing light and electron microscopic techniques. The fibrocollagenous tissue complexes after 4 to 16 weeks of development demonstrated highly ordered lamellations made of zones consisting primarily of fibroblasts and zones consisting primarily of collagenous fibers. The development of the ordered lamellations is referable to specific fibrillogenic activities by the constituent fibroblasts. The initial role of the fibroblast in fibrillogenesis is indicative of an apocrine-like secretory process followed by a holocrine-like role which results in cytodestruction and concurrent formation of an avascular collagenic tissue referable to an organizing cicatrix in a healing wound.

MR imaging of the normal shoulder: variants and pitfalls.

In 30 volunteers with normal shoulders, the following conclusions were made with regard to normal anatomic features at magnetic resonance (MR) imaging: (a) The supraspinatus tendon has low signal intensity, except for a 1-cm area with intermediate signal intensity in the region of the "critical zone." (b) The deltoid tendon attachment on the inferior surface of the acromion may simulate a subacromial spur if not imaged in continuity. (c) Fluid in the long head of the biceps tendon sheath is normal if not completely surrounding the tendon. (d) The anterolateral branch of the anterior humeral circumflex vessels in the proximal bicipital groove adjacent to the biceps tendon mimics fluid in the tendon sheath. (e) Continuity or obliteration of the subacromial-subdeltoid bursal fat plane is an unreliable diagnostic sign since the fat plane is often focally absent. (f) Fluid is not detected in subacromial-subdeltoid bursae. (g) Undercutting of the anterior glenoid labrum by hyaline cartilage or a closely apposed middle glenohumeral ligament may simulate an anterior labral tear.