Mucosal damage is a common side effect of many cancer treatments, especially radiotherapy and intensive chemotherapy, which often induce bone marrow (BM) suppression. We observed that acetic acid- (AA-) induced mucosal damage in the colon of mice was worsened by simultaneous treatment with irradiation or 5-FU. However, irradiation 14 days prior to the AA treatment augmented the recovery from mucosal damage, suggesting that the recovery from BM suppression had an advantageous effect on the mucosal repair. In addition, BM transplantation also augmented the recovery from AA-induced mucosal damage. We further confirmed that transplanted BM-derived cells, particularly F4/80+Gr1+ “inflammatory” monocytes (Subset 1), accumulated in the damaged mucosal area in the early healing phase, and both of Subset 1 and F4/80+Gr1− “resident” monocytes (Subset 2) accumulated in this area in later phases. Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy.

Controlled immunological shock, induced by bioincompatible material apheresis for cancer (BIC MAC) therapy, produces an immunoactive status in experimental subjects. However, in order to provide a safe, painless, effective, and reproducible BIC MAC therapy, it is mandatory to provide general anesthesia with endotracheal intubation not only during apheresis procedures of 1-h duration but also for an additional 5 h. Using this procedure, there was no mortality experienced during animal experiments. Also, there were no procedurally related physical or sensory abnormalities demonstrated. This general anesthesia of 6 h covered not only the initial 30 min of the hypotension and hypoxic stages but also the recovery stages to hemodynamically normalize the experimental animals. After 6 h, the accumulated leukocytes in the lung are released back to the systemic circulation. In general, granulocytes decreased almost 100% while lymphocytes decreased only 40-50%. During these 6 h, increases of cytokines (tumor necrosis factor-α, interleukin-6, etc.) sometimes up to 1000 times occurred. After the 6-h procedure, leukocytes returned nearly to preoperative levels but tended to be continuously increased. After the fourth day, leukocyte counts more than doubled. These cellular and humoral activations were normalized after 2 weeks. These studies were conducted on six normal mongrel dogs. Currently, similar studies are planned to be conducted on tumor-bearing experimental animals. This procedurally induced immunoactivation by apheresis may be able to produce effective apoptosis in malignant tumor cells.

As a therapeutic VAD to be combined with drugs, apheresis, and cellular implants, it is advisable to develop a wearable VAD for less than 6 months of application. Such an example was shown by describing the therapeutic BCM Gyro centrifugal VAD.

Our previous studies concluded Egyptian cotton was the most appropriate material for making a second generation granulocytapheresis (G-CAP) column as structural dimensions of the cotton fibers are able to attract granulocytes. Unfortunately, it is considered to be blood incompatible as its fibers are of non-synthetic origins. In this study we examined the alteration of the removal rates of blood cells with different surface modifications of Egyptian cotton to enhance its blood compatibility. The surface-modified cotton fibers were compared after three kinds of combination treatments. There were no differences in the removal rates of white blood cells (WBCs) and particularly neutrophils with the use of three kinds of biolized cottons. Next, an ex vivo animal study with a healthy dog was performed with the prototype of the G-CAP column. The dog's blood pressure (BP) decreased to approximately 80% of the initial values of BP at 20 min after the start of the extracorporeal circulation. The decrease in BP gradually reverted to normal. WBCs and particularly neutrophils decreased significantly at 15 min after the start of the extracorporeal circulation and remained low during the extracorporeal circulation. The ability of this column to remove WBCs was maintained during extracorporeal circulation. Especially, neutrophils at the inlet of the column were thoroughly removed for 1 h. Based upon these results, a second generation G-CAP column could be fabricated with Egyptian cotton and applied for clinical use on the condition that the biocompatibility of the Egyptian cotton needs to be improved by the appropriate biolization method.