PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “BCG”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1982

Immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma: a preliminary report.

Cows of the Dutch Frisian and Maas-Rijn-IJssel breed with histologically confirmed ocular squamous cell carcinoma showed complete regression of the primary tumor in 70 or 60% of the cases after intralesional injection of a BCG cell wall or live BCG vaccine, respectively. Recurrence of the tumor was observed in 57% of the animals treated with BCG cell walls and in 25% of the animals treated with live BCG vaccine. Spontaneous regression was seen in 20% of the untreated cows. In a second control group, radical surgery, the most successful treatment for primary stage I tumors in humans, resulted in a 90% cure. Influence of immunotherapy on metastases could not yet be fully evaluated. White blood cell counts were not changed after therapy. It was not possible to link a favorable response to BCG therapy with the intensity of the delayed type hypersensitivity (DTH) reaction to purified protein derivative of mycobacteriae (PPD) or the formation of antibodies to BCG as determined by a micro-enzyme-linked immunosorbent assay. However, in animals that showed tumor regression, the DTH reaction to PPD had a tendency to persist for a longer period of time. It was concluded that 1) block resection was the best method of treatment for this tumor, 2) a single intralesional injection of a BCG cell wall vaccine was as effective as live BCG vaccine in the induction of complete regression of the primary tumor, 3) in this preliminary study BCG cell wall vaccine was less effective than live BCG vaccine in the prevention of recurrence, and 4) this naturally occurring tumor model is well suited for the study of the influence of BCG immunotherapy in a primary stage I tumor.

Animals↗
PubMed2002

Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice.

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis showed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the antimetastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

Angiogenesis Inhibitors↗
PubMed2005

Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice.

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability of two new TB vaccine candidates, heat-killed BCG (H-kBCG) and arabinomannan-tetanus toxoid conjugate (AM-TT), given intransally in a novel Eurocine adjuvant, to boost a primary BCG-induced immune response and to improve protection. Young C57BL/6 mice were vaccinated with conventional BCG and, 6 months later, boosted intranasally with adjuvanted H-kBCG or AM-TT, or subcutaneously with BCG. Ten weeks after the booster, mice were challenged intravenously with M. tuberculosis (Mtb) strain H37Rv. In spleens, there was a significant reduction of cfu counts in mice boosted with either H-kBCG or AM-TT vaccines compared to the non-boosted BCG-vaccinated mice. None of the boosting regimens significantly reduced bacterial loads in lungs, compared to non-boosted BCG vaccination. However, the extent of granulomatous inflammation was significantly reduced in the lungs of mice that received two of the booster vaccines (AM-TT and conventional BCG), as compared with sham-vaccinated mice. All boosted groups, except for mice boosted with the AM-TT vaccine, responded with a proliferation of spleen T cells and gamma interferon production comparable to that induced by a single BCG vaccination.

Administration, Intranasal↗
PubMed2006

Oral vaccination of mice with lipid-encapsulated Mycobacterium bovis BCG: Effect of reducing or eliminating BCG load on cell-mediated immunity.

Oral delivery of lipid-encapsulated BCG represents an effective method for vaccination against tuberculosis (Tb). This method establishes live, replicating BCG in the lymphatic tissues of the alimentary tract, and promotes systemic-level cell-mediated immunity (CMI) and consequent protection against virulent mycobacterial challenge. Here, we investigated the effects of reducing or eliminating the BCG load on CMI responses in mice. Mice receiving a standard immunising dose of approximately 10(7) BCG (range, 1-5 x 10(7)) developed mycobacterial antigen-specific lymphocyte transformation (LT) responses, as well as interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) secretion, at 8 and 18 weeks post-oral vaccination. These responses were concurrent with establishment of viable, replicating BCG in the alimentary tract lymphatics in over 90% of cases. Reducing the immunising dose by 10-fold reduced the magnitude of CMI, concurrent with abridged establishment of BCG in the lymphatics; reducing the dose 100-fold ablated BCG establishment, and diminished the production of IFN-gamma by antigen-stimulated lymphocytes of these mice. In mice immunised using the standard dose, replicating BCG were eliminated from the alimentary tract lymphatics using selective antibiotics. Interestingly, while lymphocyte transformation and interleukin-2 responses remained largely unaltered in these mice, levels of IFN-gamma produced by antigen-stimulated lymphocytes were shown to be reduced significantly. This study identifies a dosage threshold for effective oral vaccination using lipid-encapsulated BCG, and furthermore highlights the requirement of on-going intra-lymphatic BCG replication for the maintenance of strong IFN-gamma production, above other indicator CMI responses.

Adjuvants, Immunologic↗
PubMed1993

Dissecting the immunobiological effects of Bacillus Calmette-Guérin (BCG) in vitro: evidence of a distinct BCG-activated killer (BAK) cell phenomenon.

Several immunobiological effects of intravesical bacillus Calmette-Guérin (BCG) during immunotherapy of superficial bladder cancer have been suggested as possible mediators of the mode of action. In an attempt to elucidate which of these effects is relevant to tumoricidal activity, an in vitro cytotoxicity assay was employed in which the direct effects of BCG and of cytokines against four transitional carcinoma cell lines were studied. Furthermore, peripheral blood mononuclear cells (PBMNC) were analyzed for their cytotoxic potential against these target cells. We found that none of the cytokines interleukin-1, interleukin-2, interferon-gamma, tumor necrosis factor alpha, lymphotoxin, or BCG alone were cytotoxic against the bladder carcinoma cell lines. However, a pronounced cytotoxicity against these targets resistant to natural killer cells could be induced in PBMNC by coincubation with viable BCG. We termed this the BCG-activated killer (BAK) cell phenomenon. In contrast to lymphokine-activated (LAK) cells, these BAK cells needed prolonged activation for 7 days and did not enhance the cytotoxicity against K562 target cells sensitive to natural killer cells. Nonviable, heat-inactivated BCG was significantly less effective, and sonificated fractions of BCG were not effective in stimulating PBMNC towards BAK cell activity. In vitro dissection of effects observed during BCG intravesical therapy may give more insight into the mode of action of BCG and may help to separate primary tumoricidal effector mechanisms from secondary concomitant phenomena. Further characterization of the BAK cell may result in an improvement of intravesical BCG immunotherapy.

BCG Vaccine↗
PubMed1990

Regulation of Mycobacterium bovis BCG and foreign body granulomas in mice by the Bcg gene.

Natural bactericidal resistance to Mycobacterium bovis BCG is under the control of a single gene, designated Bcg. Lung granuloma formation in susceptible (Bcgs) and resistant (Bcgr) mice was studied in two sets of Bcg-congenic systems, namely, the BALB/c (Bcgs)-C.D2 (BALB/c.Bcgr) pair and the B10.A (Bcgs)-B10.Ar (Bcgr) pair, by using BCG as well as foreign body granuloma-inducing agents (dextran beads). Large granulomas of the lung induced by the intratracheal instillation of either BCG or dextran beads developed in Bcgs mice. In contrast, minimal inflammation was produced in Bcgr mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced by Bcgs mice by either BCG or dextran beads contained high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) or interleukin-4 (IL-4) activity. Very low IL-1 activity was detected in extracts from Bcgr mice injected with BCG and dextran beads. The activity of IL-1 was correlated closely with the activity and size of the granulomatous inflammation in mice. These results suggest that pleiotropic effects of the Bcg gene are involved in the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that monokines participate in granuloma formation.

Animals↗
PubMed1978

Inhibition and promotion of tumor growth by BCG: evidence for stimulation of humoral enhancing factors by BCG.

Effects of pretreatment with BCG, strain Japan, on tumor growth were studied using a transplatable methylcholanthrene (MCA)-induced fibrosarcoma in C3H/He mice. Injection of BCG7 weeks before tumor inoculation at a site distant from the tumor caused a slight inhibition of tumor growth. A low dose of tumor cells did not grow at the BCG-primed site when BCG was injected 7 and 11 weeks before the tumor. When a high dose was inoculated into the BCG-primed site, inhibition of the primary tumor occurred in mice which had received BCG 7 weeks previously, but the number of distant metastases in the popliteal lymph node and the lungs was increased in mice pretreated with BCG at any time. Furthermore, post treatment with BCG at a site distant from the tumor caused promotion of tumor growth. Enhanced antibody formation and suppression of delayed type hypersensitivity (DTH) occurred in tumor-bearing mice. BCG treatment of such mice caused a vigorously enhanced antibody formation and a marked suppression of DTH. The sera from tumor-bearing mice enhanced tumor growth. Tumor growth was suppressed in splenectomized mice. These findings suggested that antibodies against tumor-specific antigens enhanced tumor growth in this system and that BCG treatment of tumor-bearing mice stimulated formation of antibodies probably acting as blocking factors.

Animals↗
PubMed1985

[Suppression of the parasitemia in rodent filariasis (Litomosoides carinii) by immunization with BCG and microfilaria. II. Intravenous BCG application].

By intravenous (i.v.) inoculation of living tuberculosis bacteria (BCG) non-specific resistance to microfilariae of Litomosoides carinii (Filarioidea) is induced in cotton rats. This is only possible using the preparation "Immune-BCG Pasteur F" (suspended germs), but not with "Vaccin-BCG pour scarifications" (lyophilized tuberculosis bacteria). After inoculation of Immune-BCG, followed by a challenge infection by 60 infective larvae 6 weeks later, a patent infection develops. However, the level of microfilaraemia is constantly lower than in the control. After challenge infection 12 weeks later, this effect has disappeared. Immune-BCG has no influence on the worm load or the output of microfilariae by the adult worms. If i.v. inoculation of Immune-BCG is combined with a subcutaneous injection of specific antigen--living embryos from the uteri of adult worms--the BCG-activated immune system undergoes specific sensitization. Upon challenge infection 6 weeks later, the microfilaraemia is completely suppressed, but the worm load and production of microfilariae by the adult female worms are normal. If Immune-BCG is injected i.v. 3 days before intraperitoneal injection of freeze-killed microfilariae, there is still constantly reduced microfilaraemia when challenge infection follows 12 weeks later. Obviously, the effect of this relatively weak antigen may be increased by BCG stimulation.

Animals↗
PubMed2000

Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model.

Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette-Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recombinant BCG vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of TB. We have tested the efficacy of the two strains in the highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB. Animals immunized with the recombinant BCG vaccines and challenged by aerosol with a highly virulent strain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG vaccine counterparts. Statistically, these differences were highly significant. Paralleling these results, at necropsy, animals immunized with the recombinant BCG vaccines had fewer and smaller lesions in the lung, spleen, and liver and significantly less lung pathology than animals immunized with the parental BCG vaccines. The recombinant vaccines are the first vaccines against TB more potent than the current commercially available BCG vaccines, which were developed nearly a century ago.

Animals↗
PubMed1999

Results of a European comparative randomized study comparing oral bropirimine versus intravesical BCG treatment in BCG-naive patients with carcinoma in situ of the urinary bladder. European Bropirimine Study Group.

OBJECTIVES: This European phase III clinical trial was part of an intercontinental study which was closed prematurely by the sponsor. The study was designed to compare the effects of oral bropirimine with intravesical BCG, the current standard treatment in patients with newly diagnosed bladder carcinoma in situ (CIS). METHODS: A total of 55 BCG-naive patients with bladder CIS were randomized to receive bropirimine (n = 27) or BCG (n = 28). Bropirimine was orally administered at a dose of 3 g/day for 3 consecutive days with a 4-day drug-free interval for up to 1 year. BCG-Tice instillations were administered weekly for 2 x 6 weeks. Both biopsies and cytology had to be negative for the patient to be considered a complete responder (CR). RESULTS: The percentage of dropouts for all of the adverse events was 4% for bropirimine and 14% for BCG. The most frequently reported local events in the bropirimine- versus the BCG-treated group were irritative complaints, 64 vs. 89% (p = 0.03) and hematuria, 24 vs. 61% (p < 0.01). The most frequently reported systemic events in the bropirimine- versus the BCG-treated group were fever 4 vs. 21%, flu syndrome 24 vs. 7%, headache 28 vs. 11% and nausea 24 vs. 11% (all p > 0.05). A total of 92% of the patients treated with bropirimine had a CR with a mean duration of 12.6 months (95% CI 9.2-15.9). In the BCG group, all of the patients had a CR with a mean of 12.3 months (95% CI 8.5-16.0). CONCLUSIONS: This study shows that bropirimine, an orally administered drug that can be self-administered to outpatients with more acceptable local toxicity compared to BCG, could be an effective first-line therapy in patients with CIS of the urinary bladder. Continued investigation of bropirimine is warranted to increase its clinical utility.

Adjuvants, Immunologic↗
PubMed2000

Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

Groups of rhesus monkeys were vaccinated and boosted with Mycobacterium bovis bacillus Calmette Guerin (BCG) or BCG plus low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M. leprae (ML) challenge, these and unvaccinated, unchallenged control monkeys were observed longitudinally for approximately 3 years. Vaccination with BCG plus HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to lepromin, which returned to baseline post-boosting and post-live-ML-challenge, minimally reappearing significantly 2 years post-ML-challenge. Vaccination with BCG failed to stimulated positive blastogenic responses to lepromin before ML-challenge but small, marginally positive, intermittent responses were seen post-ML-challenge. Compared to the unvaccinated ML-challenged group, significant increases in the numbers of blood CD4+ and CD8+ T-cell subsets and an increased CD4+:CD8+ ratio were observed in both BCG plus HKML-vaccinated, ML-challenged groups, but not in the BCG-only-vaccinated, ML-challenged group. CD4+CD29+ and CD4+CD45RA+ subset numbers increased significantly over time in only the BCG plus LD HKML-vaccinated, ML-challenged group. Compared to unvaccinated, ML-challenged groups, vaccination with BCG or BCG plus HKML followed by ML-challenge produced lower IgM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody ratios and protected rhesus monkeys from clinical leprosy, consistent with prior observations that low IgM:IgG anti-PGL-I responses correlated with resistance to and protection from leprosy.

Adjuvants, Immunologic↗
PubMed2003

Management of bacillus Calmette-Guerin (BCG) refractory superficial bladder cancer: results with intravesical BCG and Interferon combination therapy.

INTRODUCTION AND OBJECTIVE: BCG is the most efficacious intravesical treatment for superficial bladder cancer. However, 30%-40% of tumors are refractory. BCG failure is an indication for cystectomy but several salvage intravesical (IVe) strategies have been proposed. Early results with reduced dose BCG in combination with IFN-a in patients are currently the most promising. We have adopted this approach and now report our preliminary results. This is the first report of this salvage therapy from Canada, the birthplace of IVe BCG therapy for superficial bladder cancer. METHODS: The "O'Donnell protocol" of reduced dose IVe BCG plus IFN-a was followed in 12 patients with BCG refractory superficial transitional cell carcinoma. A retrospective review of the efficacy and toxicity of the treatment was conducted. RESULTS: One year from induction therapy with salvage BCG/IFN-a, 6 of the 12 (50%) of patients were tumor free. Of the six recurrences, 3(50%) did not respond to the IVe therapy and had residual/recurrent tumor at the first follow-up visit. Risk factors for treatment failure were identified. The combinative therapy was well tolerated with minimal toxicity compared to previous full dose BCG. CONCLUSION: Our 12 month data with reduced dose IVe BCG plus IFN-a salvage therapy for BCG refractory superficial TCC confirm previous reports of >50% complete response rates. We need longer follow up in a larger patient population to determine the durability of this promising therapy in patients who would otherwise undergo radical cystectomy.

Antineoplastic Agents↗
PubMed1991

Intravesical BCG administration in the guinea pig. II. Immunohistochemical characterization of cellular infiltrate after one or two cycles of intravesical BCG.

The intravesical administration of bacillus Calmette-Guérin (BCG) is used as an adjuvant therapy after transurethral resection for superficial bladder cancer in man. The aim of this study was to characterize with monoclonal antibodies the cellular infiltrates in the bladder wall occurring after one or two cycles, each comprising six weekly intravesical BCG administrations in guinea pigs. BCG-RIVM and BCG-TICE were instilled once a week in undamaged bladders at weeks 1-6 and 11-16, respectively, and retained in the bladder for 1 h. Autopsy was performed 1 week after the last BCG administration at weeks 7 and 17. By routine histology, a single BCG course induced scattered focal infiltrates consisting of minor to severe accumulations of mononuclear cells. After two cycles of BCG, a much more severe inflammatory reaction sometimes occupying almost the total bladder mucosa was noted. The major component of this inflammation was mononuclear cells, mainly lymphocytes, while typical BCG granulomas were occasionally observed. In general, the epithelial layer of the bladder showed no visible alterations. Immunohistochemical staining showed that the majority of mononuclear cells present in the infiltrate were T-cells. Widely scattered B-cells and macrophages were also present, but were much fewer in number than the T-cells. In general, T-helper/inducer cells were more frequent than T-suppressor/cytotoxic cells. Pseudofollicles, also noted after H&E staining, consisted mainly of B-cells. The second series of BCG administrations produced pseudofollicles in the infiltrates in all animals investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

Mode of immunopotentiating action of BCG: persistence and spread of BCG infection.

The mode of action of BCG, strain Japan was investigated using the immune response to sheep red blood cells (SRBC) as an indicator system. When SRBC were injected into the BCG-primed foot pad, the direct plaque forming cells (PFC) and the effector cells responsible for delayed type hypersensitivity (PTH) were produced in various lymphoid organs widely distributed. Furthermore, bacterial counts in the draining popliteal lymph node and the spleen in the mice inoculated with BCG into the hind foot pad suggested that a local infection with BCG has spread to a generalized systemic infection of lymphoid tissues with time. Enhancement of DTH response to SRBC was induced when the mice previously infected with BCG were inmunized with SRBC mixed with purified protein derivative (PPD). These findings suggested that nonspecific augmentation of immune response with BCG was due to a generalized systemic activation of lymphoid system by BCG infection and the long lasting effect of immunopotentiation with BCG was due to persisting BCG infection in the lymphoid tissues.

Animals↗
PubMed1981

Mechanism of action of BCG-tumor cell vaccines in the generation of systemic tumor immunity. I. Synergism between BCG and line 10 tumor cells in the induction of an inflammatory response.

The intradermal injection of a vaccine composed of 10(7) X-irradiated, syngeneic hepatocarcinoma line 10 (L10) cells admixed with 10(8) Mycobacterium bovis strain BCG into inbred Sewall Wright strain 2 guinea pigs induced a local acute and then chronic inflammatory response. Cellular analysis of enzymatically dispersed dermal vaccination sites and regional lymph nodes revealed quantitative differences between the cellular infiltrate induced by a mixed BCG-tumor cell vaccine and the inflammation induced by either 10(8) BCG alone or 10(7) tumor cells alone. Analysis of dermal sites from days 1 through 4 following vaccination showed that sites receiving the BCG-tumor cell vaccine contained twofold to fourfold more cells than did those induced by BCG alone and more than fourfold the number of cells induced by L10 cells alone. These results indicated that there was a synergistic interaction between BCG and L10 cells in the induction of an inflammatory response at the site of vaccination. Analysis of the superficial distal axillary lymph nodes draining the site of vaccination revealed a similar synergistic interaction between BCG and L10, such that lymph nodes draining vaccination sites had a greater total cellular content than that induced by either BCG or L10 cells administered separately. When two other tumors, also syngeneic to strain 2 guinea pigs, were tested for their ability to interact synergistically with BCG to elicit an inflammatory response, it was found that the antigenically distinct hepatocarcinoma line 1 tumor also shared this characteristic with L10, whereas the L2C B-cell leukemia did not.

Animals↗