• Tuberculosis and Respiratory Diseases
• /
• v.50 no.3
• /
• pp.367-372
• /
• 2001

Bacillus Calmette-Guerin(BCG) has been widely used for the prophylaxis of superficial bladder tumor recurrence and for the treatment of bladder carcinoma in situ. More than 95% of patients who receive BCG instillation tolerate the treatment well and side reactions have been reported in less than 5% of patients. Most side effects are minor and self-limiting. However, a rare occurrence of severe systemic reactions have been reported. Among the severe systemic reactions, hypersensitivity pneumonitis should be considered in patients with pneumonic complications after BCG instillation in cases where the culture for mycobacteria is negative in the sputwn, brochoalveolar lavage and blood specimen. In addition, a fiberoptic bronchoscopy with transbronchial lung biopsy demonstrates a fibrosis of the alveolar septums, where there is and an increased lymphocyte count with out tuberculous inflammatory changes, the and CD4 : CD8 ratio is increased and no symptomatic response to antituberculosis chemotherapy is observed. Here we report a 68 years old man with interstitial pneumonitis following intravesical BCG instillation.

• Parasites, Hosts and Diseases
• /
• v.47 no.2
• /
• pp.175-177
• /
• 2009

Cancer is the main cause of death in developed countries. However, in underdeveloped countries infections and parasitic diseases are the main causes of death. There are raising scientific evidences indicating that parasitic infections induce antitumor activity against certain types of cancers. In this study, the effects of Toxoplasma gondii and Toxocara canis egg antigens in comparison with Bacillus Calmette Guerin (BCG) (known to have anticancer distinctive) on WEHI-164 fibosarcoma transplanted to BALB/c mice was investigated. Groups of 6 male BALB/c mice injected with T. gondii antigen, BCG, or T. canis egg antigen as case groups and alum alone as control groups. All mice were then challenged with WEHI-164 fibrosarcoma cells. The mice were examined for growth of the solid tumor and the tumor sizes were measured every other day up to 4wk. The mean tumor area in T. gondii, BCG, or alum alone injected mice in 4 different days of measurements was $25\;mm^2$, $23\;mm^2$, and $186\;mm^2$ respectively, Also the mean tumor area in T. canis injected mice in 4 different days was $25.5\;mm^2$ compared to the control group (alum treated) which was $155\;mm^2$. T. gondii parasites and T. canis egg antigens induced inhibition of the tumor growth in the fibrosarcoma mouse model. We need further study to clarify the mechanisms of anti-cancer effects.

• Korean Journal of Veterinary Research
• /
• v.52 no.2
• /
• pp.89-97
• /
• 2012

Mycobacterial cell-wall skeleton (CWS) is an immunoactive and biodegradable particulate adjuvant and has been tried to use for immunotherapy. The CWS of Mycobacterium bovis bacillus Calmette-Guerin (BCG-CWS) was studied as an universal vaccine vehicle for antigen conjugation, to develop potentially effective and safe vaccine. Although a variety of biological activities of BCG-CWS have been studied, the effects of BCG-CWS on spleen cells are not fully elucidated. Using MTT assay and trypan blue exclusion test, we found that BCG-CWS significantly enhanced the viability and proliferation of cells. Multiple clusters, indicating proliferation, were observed in BCG-CWS-treated spleen cells and surface marker staining assay revealed that BCG-CWS promoted the proliferation of $CD19^+$ B lymphocyte rather than $CD4^+$ or $CD8^+$ T lymphocyte. In addition, BCG-CWS up-regulated the expression of anti-apoptotic molecules such as bcl-2, bcl-xL. BCG-CWS increased the surface expression of CD25 and CD69 as well as IL-2 production of spleen cells, suggesting increased activation. Furthermore, BCG-CWS enhanced the antigen-specific cell proliferation and interferon-gamma production of spleen cells. Taken together, these results demonstrate the immunostimulatory effects of BCG-CWS on spleen cells via multiple mechanisms, providing valuable information to broaden the use of BCG-CWS in clinical and research settings.

• IMMUNE NETWORK
• /
• v.23 no.2
• /
• pp.16.1-16.19
• /
• 2023

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4⁺ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

• Applied Microscopy
• /
• v.35 no.3
• /
• pp.153-163
• /
• 2005

This experiment was performed to evaluate the morphological responses of the gastric chief cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG (Bacillus Calmette-Guerin). Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (experimental control group and BCG treated group). In the experimental groups, each mouse was inoculated with $1x10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the last injection, each mouse was sacrificed. Pieces of the tissue were taken from the stomach, prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. The ultrathin sections were stained with uranyl acetate and lead citrate. The size of zymogen granule and the size of the mitochondrion of the gastric chief cells were observed and calculated. In the BCG treated group, most chief cells did not show any difference in ultrastructure, except that myelin figures were more frequently observed, in comparison with that of nornmal control group. The size of zymogen granule in the gastric chief cells of normal control, experimental control and BCG-treated groups were $0.98({\pm}0.108){\mu}m,\;1.05({\pm}0.092){\mu}m\;and\;0.93({\pm}0.053){\mu}m$, respectively. And the mitochondrial size of the gastric chief cells of normal control, experimental control and BCG-treated groups were $0.80({\pm}0.130){\mu}m,\;0.83({\pm}0.143){\mu}m\;and\;0.72({\pm}0.078){\mu}m$, respectively. From the above results, it was concluded that BCG may slightly suppress function of the gastric chief cells.

• Applied Microscopy
• /
• v.37 no.3
• /
• pp.157-166
• /
• 2007

This experiment was performed to evaluate the ultrastructural responses of the absorptive cells in the appendix of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG (Bacillus Calmette-Guerin). Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (experimental control group and BCG treated group). In the experimental groups, each mouse was inoculated with $1{\time}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.5mL of saline or BCG (0.5 mL/25gm B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8CFU$) were injected subcutaneously to the animals every other day. The day following the last injection, each mouse was sacrificed. Pieces of the tissue were taken from the appendix, prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. The ultrathin sections were stained with uranyl acetate and lead citrate. In the normal control, experimental control and BCG treated mice, general morphology of the absorptive cells of appendix were similar. But myelin figures and intramitochondrial dense granules were more frequently observed in the absorptive cells of BCG treated mice than normal control ones. Above results show that BCG did show slight ultrastructural alterations in the absorptive cell of the appendix. These results that BCG may slightly suppress function of the absorptive cells of the appendix.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.6
• /
• pp.869-878
• /
• 1999

Intravesical instillation of the bacillus Calmentte-Gu$\acute{e}$rin(BCG), an attenuated strain of Mycobacterium bovis, is an approved method for the treatment of superficial bladder cancer. Because BCG is a living organism, the potential for infection exists. BCG is generally well tolerated, with complications in less than 5% of those treated with use of current practices. The most frequent symptoms of toxicity associated with intravesical BCG immunotherapy include bladder irritation, frequency, and dysuria. Systemic reactions are less common but more serious than local side effects, and include fever, chills, malaise, rash, hepatitis, pneumonitis, arthritis and sepsis. In rare cases, BCG treatment can result in a systemic infection that requires antituberculous therapy. The pulmonary toxicity that results from intravesical BCG treatment is generally characterized by one of two types : systemic allergic reaction with pulmonary reticulonodular opacities depicted on chest radiographs with cellular findings consisting of activated lymphocytes, and actual BCG mycobacteremia with a miliary pattern depicted on chest radiographs and granuloma formation which rarely results in positive acid-fast stain or culture results. Recently we experienced two types of pulmonary complications following intravesical BCG immunotherapy in patients with superficial bladder cancer. We report two cases with a review of literatures.

• Applied Microscopy
• /
• v.39 no.3
• /
• pp.205-218
• /
• 2009

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group and BCG-treated group). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of 0.7 ${\mu}Ci/g$ of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and gastric tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab., England) in a dark room. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. And for electron microscopic observation, gastric tissues were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. On the light microscopic study, gastric mucosae had no morphological changes following the injection of BCG. On the electron microscopic study, in the BCG-treated mice, myelin figures and multivesicular bodies within the gastric epithelial cells were observed more frequently than in those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 380.2 (${\pm}31.35$), 426.1 (${\pm}28.43$) and 301.8 (${\pm}34.63$), respectively. In the BCG-treated mice, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control and tumor control ones. From the above results, BCG may suppress the DNA synthesis of the gastric epithelial cells, but does not results severe fine structural defect on the gastric epithelial cells. These results suggest that BCG is expected as one of the effective supplemental anticancer drugs.