romurtide and Lung-Neoplasms

N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys (L18), romurtide) is a synthetic muramyl dipeptide derivative, and has immunomodulating activities including activation of cells of monocyte-macrophage lineage. We examined the effect of intrapleural instillation of MDP-Lys (L18) against malignant pleurisy associated with lung cancer. Six patients with cytologically-positive malignant pleural effusion (four with adenocarcinoma, one with small cell carcinoma and one with large cell carcinoma) were treated with single intrapleural instillation of MDP-Lys (L18) of 200 microg. Clinically, no reaccumulation of pleural effusion for at least 4 weeks was observed in four patients. No major side effects were observed. Total cell number elevated remarkably 4 h after instillation, and main increased population was that of neutrophils. Levels of chemotactic cytokines, such as interleukin (IL)-8, and monocyte chemotactic protein (MCP)-1 and levels of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, elevated in pleural effusion, and peak IL-1beta and IL-6 levels tended to be higher in clinical responders than non-responders. These results suggest MDP-Lys (L18) instilled by intrapleural route had a potential local immunomodulatory activity. Further study is warranted to further determine the critical factors which correlate with the clinical response.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Aged; Cytokines; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pleural Effusion, Malignant; Pleurisy; Treatment Outcome

The effectiveness of thrice-weekly injection of Romurutide for leukocytopenia due to radiation therapy was analyzed. Twenty-two patients were randomly divided into two groups. Ten of group A cases were injected 3 times per week 10 times (3 weeks) and 12 of group B cases were injected 5 times per week 10 times (2 weeks). White blood cell counts and neutrophil numbers in group A were almost the same as in group B at day-3 and day-8, and those in group A were more than in group B at day-15 and day-22, although there were no statistical significances. Lymphocyte percentages, monocyte percentages and platelet cell counts between groups showed no differences. Injections were stopped in 3 cases due to fever (2 in group A, 1 in group B). The effects were recognized in nineteen cases (excluding above 3 cases). The effect of this thrice-weekly injection method during the injection period was the same or more than with 5 injections/week, and the period of the former was 50% longer. The 3 weekly injection method is more effective for prophylaxis of leukocytopenia.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Breast Neoplasms; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasms; Uterine Cervical Neoplasms

N2-[(N-Acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a derivative of muramyl dipeptide (MDP), is known to promote recovery of peripheral leukocyte and platelet counts by inducing cytokines, especially colony stimulating factor (CSF) in myelosuppression secondary to anticancer therapy. This paper reviews the results of a double-blind comparative study on lung cancer patients, administered either 200 micrograms or 20 micrograms of muroctasin for 6 days post-chemotherapy. It demonstrates the efficacy of muroctasin, at 200 micrograms doses levels only, in promoting early recovery of leukocyte and platelet counts and hence the potential for earlier initiation of chemotherapy cycles. The most common side effect encountered during the study was transient fever.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Antineoplastic Agents; Biological Factors; Cytokines; Double-Blind Method; Humans; Leukopenia; Lung Neoplasms; Neutrophils; Platelet Count; Randomized Controlled Trials as Topic; Thrombocytopenia

N2-[(N-Acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a derivative of muramyl dipeptide, is known to have the activity to augment the number of white blood cells (WBC) via colony-stimulating factor. Muroctasin has been expected to be applied to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by the combination regimens of chemotherapy, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on Days 4, 7 and 15 after commencement of the study. WBCs in H and L groups were recovered greater than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin treated groups. The portion of immature neutrophil in the bone marrow was also increased by muroctasin treatment. A restorative effect on WBC and neutrophil counts was also confirmed only in the second course of H group. On the other hand, fever and pain in the injected site as side effects were common in the H group and L group in both of courses. In this study, the usefulness of muroctasin in leukopenia was suggested when administered at dosages of 200 micrograms for 6 days.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Aged; Antineoplastic Agents; Bacterial Infections; Blood Cell Count; Bone Marrow; Female; Humans; Leukocyte Count; Leukopenia; Lung Neoplasms; Male; Middle Aged

Muroctasin, a derivative of MDP, is known to augment the number of WBC via colony-stimulating factor. Muroctasin has been expected to be promising for application to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by chemotherapy combination, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on days 4, 7 and 15 after commencement of the study. WBCs in H and L groups showed greater recovery than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin-treated groups. A portion of immature neutrophil in bone marrow was also increased by muroctasin treatment. In the present study, the usefulness of muroctasin in leukopenia was indicated when administered at dosages of 200 micrograms for 6 days.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Random Allocation; Vincristine; Vindesine

MDP-Lys (N2-[(N-acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine), a macrophage activator, is a lipophilic derivative of muramyl dipeptide (MDP). Multilamellar liposome incorporated MDP-Lys was prepared using phosphatidylcholine and phosphatidylserine by conventional film method, and its inhibitory effect on lung metastasis was compared with MDP-Lys as a solution in hamster's osteosarcoma. The lung metastatic rates after transplantation of the tumor to a lower extremity, in which the extremity was amputated 3 weeks later, were 50% and 100% 3 and 7 weeks, respectively, after transplantation. The rates after amputation were reduced by the treatment with MDP-Lys proportionally to the logarithmic MDP-Lys dose, and the rates 7 weeks after transplantation were 55% and 60%, respectively, in the MDP-Lys solution (50 microg/day) and liposomal MDP-Lys (20 microg twice/week) groups. Fifty percent of hamsters treated with liposomal MDP-Lys survived for more than 6 months. Considering that hamsters had a lung metastasis rate of 50% before MDP-Lys treatment, liposomal MDP-Lys given at a dose of 20 microg twice/week was effective for inhibiting lung metastasis at a far lower dose of MDP-Lys than that given as a solution (40 microg vs. 350 microg per week). No significant side effect of liposomal MDP-Lys, as evaluated by the comparison of body weight changes among differently treated hamsters, was detected. This greater inhibitory effect of liposomal MDP-Lys can be considered to be due to the longer retention of the liposomal form in the lung.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Body Weight; Bone Neoplasms; Cricetinae; Liposomes; Lung Neoplasms; Male; Mesoderm; Neoplasm Transplantation; Osteosarcoma; Survival Analysis; Time Factors

Muramyl dipeptide (MDP), derived from the major constituent of bacterial cell walls, can augment host defense mechanisms, and romurtide [MDP-Lys (L18)], a synthetic MDP derivative, is thought to be more potent than other MDP derivatives. Therefore, we evaluated whether romurtide can bolster the immune defense mechanisms of the lung. We compared the functions of peripheral blood leukocytes with those of broncho alveolar lavage fluid cells (BALF cell) in DA rats and in patients with lung cancer who were treated with radiation. The results indicate that romurtide can increase the antibacterial activity of BALF cells preferentially and that this adjuvant therapy can help to prevent respiratory infections.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Bronchoalveolar Lavage Fluid; Female; Humans; Immunity, Innate; Lung; Lung Neoplasms; Male; Rats; Rats, Inbred Strains; Stimulation, Chemical

The antimetastatic effects of MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide (MDP), against three different types of highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 T lymphoma, were examined in C57BL/6, Balb/c and CDF1 mice, respectively. The administration of 100 micrograms of MDP-Lys(L18) 2 or 4 days before tumour inoculation led to a significant decrease in lung metastasis of B16-BL6 melanoma or colon 26-M3.1 carcinoma cells. MDP-Lys(L18) was also effective in the inhibition of liver metastasis of L5178Y-ML25 lymphoma cells by administration 2 or 4 days before tumour inoculation. The prophylactic effect of 100 micrograms of MDP-Lys(L18) on tumour metastasis was evident for the different administration routes, i.e. subcutaneous, intravenous or intranasal injection, or oral administration. It is of prime interest that oral administration of 1 mg of MDP-Lys(L18) induced a significant decrease in lung metastasis of B16-BL6 melanoma cells. Administration of MDP-Lys(L18) 4 days before assay led to induction of tumoricidal activity by peritoneal macrophages and growth inhibition by the sera against B16-BL6 or L929 cells. When MDP-Lys(L18) was subcutaneously administered five times after tumour inoculation to test therapeutic effect in an experimental and spontaneous metastasis model using B16-BL6 melanoma, the consecutive administrations of MDP-Lys(L18) significantly inhibited lung metastasis in tumour-bearing mice. These results suggest that MDP-Lys(L18) is able to enhance host resistance to reduce tumour metastasis and is a potent immunomodulating agent which may be applied prophylactically or therapeutically for the treatment of cancer metastasis.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Female; Immunotherapy; Leukemia L5178; Liver Neoplasms, Experimental; Lung Neoplasms; Macrophage Activation; Macrophages, Peritoneal; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasms, Experimental; Neoplastic Cells, Circulating; Splenic Neoplasms

The study was carried out to confirm the effect of MDP-Lys (L 18) on the neutrophil number and function in the patients with lung cancer. The patients were enrolled only in case of leukopenia (equal or less than 3,000/mm3 after anticancer chemotherapy) and subcutaneously given 200 mcg of MDP-Lys (L 18) for 7 days. Mean leukocyte counts were found to be 3,900/mm3 and 5,500/mm3 one day and one week after MDP-Lys (L 18) treatment, respectively. The rate of "markedly effective" and "effective" was 53% (8/15). Chemiluminescence by zymosan showed a significant increase after MDP-Lys (L 18) treatment. However, no change of neutrophil function was observed in the tests of chemiluminescence by phorbol myristate acetate, superoxide (O2-) production, hydrogen peroxide (H2O2) production, chemotaxis, bacterial killing and opsonization. Transient fever was observed in 6 cases and eruption accompanied with one fever case. It was concluded that MDP-Lys (L 18) could prevent infection in cancer-bearing immunocompromised patients by increasing the neutrophil number and function.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Aged; Aged, 80 and over; Drug Evaluation; Female; Humans; Immune Tolerance; Leukocyte Count; Leukopenia; Luminescent Measurements; Lung Neoplasms; Male; Middle Aged; Neutrophils