scholarly journals Microorganisms in the Treatment of Cancer: Advantages and Limitations

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Klaudia Łukasiewicz ◽  
Marek Fol
Keyword(s):  
Immune Response ◽  
Toxin Production ◽  
Anticancer Therapy ◽  
Experimental Phase ◽  
Research Directions ◽  
Standard Methods ◽  
Specific Location ◽  
Selective Elimination ◽  
Bacterial Stimulation ◽  
Methods Of Treatment

Cancer remains one of the major challenges of the 21st century. The increasing numbers of cases are not accompanied by adequate progress in therapy. The standard methods of treatment often do not lead to the expected effects. Therefore, it is extremely important to find new, more effective treatments. One of the most promising research directions is immunotherapy, including the use of specific types of microorganisms. This type of treatment is expected to stimulate the immune system for the selective elimination of cancer cells. The research results seem to be promising and show the intensive activation of the immune response as a result of bacterial stimulation. In addition, it is possible to use microorganisms in many different ways, based on their specific properties, that is, toxin production, anaerobic lifestyle, or binding substances that can be delivered to a specific location (vectors). This paper provides an overview of selected microorganisms which are already in use or that are in the experimental phase. Just like any other therapy, the use of microbes for cancer treatment also has some disadvantages. Nevertheless, this kind of treatment can supplement conventional anticancer therapy, giving cancer patients a chance and hope of recovery.

Chitosan/poly(γ-glutamic acid) nanoparticles incorporating IFN-γ for immune response modulation in the context of colorectal cancer

2019 ◽  
Vol 7 (8) ◽  
pp. 3386-3403 ◽  
Author(s):  
Flávia Castro ◽  
Marta L. Pinto ◽  
Rui Almeida ◽  
Flávia Pereira ◽  
Andreia M. Silva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Synergistic Effect ◽  
Glutamic Acid ◽  
Anticancer Therapy ◽  
Response Modulation ◽  
Ifn Γ ◽  
Immune Response Modulation

This work highlights the potential synergistic effect of chitosan/γ-PGA nanoparticles with immunomodulatory cytokines, like IFN-γ, for anticancer therapy.

scholarly journals ZupT Facilitates Clostridioides difficile Resistance to Host-Mediated Nutritional Immunity

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Joseph P. Zackular ◽  
Reece J. Knippel ◽  
Christopher A. Lopez ◽  
William N. Beavers ◽  
C. Noel Maxwell ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Potential ◽  
Neutrophil Infiltration ◽  
Toxin Production ◽  
Host Protein ◽  
Content Type ◽  
Nutritional Immunity ◽  
Clostridioides Difficile ◽  
Therapeutic Development ◽  
Dependent Growth

ABSTRACT Clostridioides difficile is a spore-forming bacterium that causes severe colitis and is a major public health threat. During infection, C. difficile toxin production results in damage to the epithelium and a hyperinflammatory response. The immune response to CDI leads to robust neutrophil infiltration at the sight of infection and the deployment of numerous antimicrobials. One of the most abundant host immune factors associated with CDI is calprotectin, a metal-chelating protein with potent antimicrobial activity. Calprotectin is essential to the innate immune response to C. difficile and increasing levels of calprotectin correlate with disease severity in both adults and children with CDI. The fact that C. difficile persists in the presence of high levels of calprotectin suggests that this organism may deploy strategies to compete with this potent antimicrobial factor for essential nutrient metals during infection. In this report, we demonstrate that a putative zinc (Zn) transporter, ZupT, is employed by C. difficile to survive calprotectin-mediated metal limitation. ZupT is highly expressed in the presence of calprotectin and is required to protect C. difficile against calprotectin-dependent growth inhibition. When competing against wild-type C. difficile, zupT mutants show a defect in colonization and persistence in a murine model of infection. Together these data demonstrate that C. difficile utilizes a metal import system to combat nutritional immunity during CDI and suggest that strategies targeting nutrient acquisition in C. difficile may have therapeutic potential. IMPORTANCE During infection, pathogenic organisms must acquire essential transition metals from the host environment. Through the process of nutritional immunity, the host employs numerous strategies to restrict these key nutrients from invading pathogens. In this study, we describe a mechanism by which the important human pathogen Clostridioides difficile resists transition-metal limitation by the host. We report that C. difficile utilizes a zinc transporter, ZupT, to compete with the host protein calprotectin for nutrient zinc. Inactivation of this transporter in C. difficile renders this important pathogen sensitive to host-mediated metal restriction and confers a fitness disadvantage during infection. Our study demonstrates that targeting nutrient metal transport proteins in C. difficile is a potential avenue for therapeutic development.

scholarly journals Evaluating the Effects of Surotomycin Treatment on Clostridium difficile Toxin A and B Production, Immune Response, and Morphological Changes

2016 ◽  
Vol 60 (6) ◽  
pp. 3519-3523 ◽  
Author(s):  
Bradley T. Endres ◽  
Eugénie Bassères ◽  
Mohammed Khaleduzzaman ◽  
M. Jahangir Alam ◽  
Laurent Chesnel ◽  
...  
Keyword(s):  
Immune Response ◽  
Clostridium Difficile ◽  
Morphological Changes ◽  
Toxin Production ◽  
Morphological Data ◽  
Growth Media ◽  
Toxin A ◽  
Content Type ◽  
Cyclic Lipopeptide ◽  
The Impact

Surotomycin is a cyclic lipopeptide in development forClostridium difficile-associated diarrhea. This study aimed to assess the impact of surotomycin exposure onC. difficiletoxin A and B concentrations and the associated changes in immune response in comparison to vancomycin and metronidazole. Time-kill curve assays were performed using strain R20291 (BI/NAP1/027) at supra-MICs (4× and 40×) and sub-MICs (0.5×) of surotomycin and comparators. Following treatment, CFU counts, toxin A and B concentrations, and cellular morphological changes using scanning electron microscopy were examined. Inflammatory response was determined by measuring interleukin-8 (IL-8) concentrations from polarized Caco-2 cells exposed to antibiotic-treatedC. difficilegrowth media. Supra-MICs (4× and 40×) of surotomycin resulted in a reduction of vegetative cells over 72 h (4-log difference,P< 0.01) compared to controls. These results correlated with decreases of 77% and 68% in toxin A and B production at 48 h, respectively (P< 0.005, each), which resulted in a significant reduction in IL-8 concentration compared to controls. Similar results were observed with comparator antibiotics. Bacterial cell morphology showed that the cell wall was broken apart by surotomycin treatment at supra-MICs while sub-MIC studies showed a “deflated” phenotype plus a rippling effect. These results suggest that surotomycin has potent killing effects onC. difficilethat results in reduced toxin production and attenuates the immune response similar to comparator antibiotics. The morphological data also confirm observations that surotomycin is a membrane-active antibiotic.

scholarly journals Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity

2021 ◽  
Vol 118 (13) ◽  
pp. e2015855118
Author(s):  
Mohamed B. F. Hawash ◽  
Joaquin Sanz-Remón ◽  
Jean-Christophe Grenier ◽  
Jordan Kohn ◽  
Vania Yotova ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Relatedness ◽  
Viral Infections ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Potential Cost ◽  
Viral Pathogens ◽  
Increased Sensitivity ◽  
Bacterial Stimulation ◽  
Interferon Responses

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

scholarly journals 2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S828-S828
Author(s):  
Travis J Carlson ◽  
Bradley T Endres ◽  
Julie Le Pham ◽  
Anne J Gonzales-Luna ◽  
Faris S Alnezary ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Outcomes ◽  
Eosinophil Count ◽  
Toxin Production ◽  
Albumin Level ◽  
Binary Toxin ◽  
Inpatient Mortality ◽  
Healthcare Facilities ◽  
Clostridioides Difficile

Abstract Background The ability of Clostridioides difficile to cause clinical disease in humans is dependent on toxin production. Significantly fewer eosinophils are seen in the peripheral blood of mice infected with a binary toxin positive (CDT+) C. difficile strain. Furthermore, the presence of CDT and eosinopenia have separately been associated with increased mortality in humans with C. difficile infection (CDI). We hypothesized that CDI due to a CDT+ C. difficile strain accompanied by peripheral eosinopenia would be associated with higher odds of inpatient mortality. Methods This multicenter, retrospective cohort study included all patients ≥ 18 years of age with toxigenic CDI in which specimen ribotype data were available as part of our ongoing surveillance study. The cohort was stratified by eosinophil count (0.0 cells/μL vs. > 0.0 cells/μL). The primary outcome was inpatient mortality. A logistic regression model was developed modeling inpatient mortality as a function of the available patient covariates. All P-values were from 2-sided tests, and results were deemed statistically significant at P < 0.05. Results A total of 688 patients from 13 institutions in six cities were included. Of those, 132 had a baseline eosinophil count of 0.0 cells/µL and 556 had a baseline eosinophil count > 0.0 cells/µL. While the odds of inpatient mortality were higher among patients with eosinopenia and those infected with a CDT+ ribotype, the combination of these variables remained an independent predictor of inpatient mortality after adjusting for CCI score, WBC count, and serum albumin level (OR, 7.84; 95% CI, 1.85–33.20; P = 0.005). Conclusion This is the first attempt to study the in vivo relationship between CDT presence, human immune response, and CDI clinical outcome. We identified an association between CDT presence with concomitant eosinopenia and worsened CDI outcomes. Healthcare facilities should consider identifying this important subset of patients at the time of CDI diagnosis. Future CDI drug development might benefit from targeting C. difficile properties that impair host immune response, which may in turn decrease adverse clinical outcomes associated with this disease. Disclosures All authors: No reported disclosures.

scholarly journals Subcutaneous paratibial fasciotomy in the treatment of chronic venous ulcer

2011 ◽  
Vol 68 (5) ◽  
pp. 430-434
Author(s):  
Ivan Lekovic ◽  
Sidor Misovic ◽  
Zoran Bjelanovic ◽  
Miroljub Draskovic ◽  
Aleksandar Tomic
Keyword(s):  
Clinical Course ◽  
Transplant Rejection ◽  
Venous Ulcer ◽  
Ulcus Cruris ◽  
Control Group ◽  
Social Significance ◽  
Standard Methods ◽  
High Incidence ◽  
Favorable Influence ◽  
Methods Of Treatment

Background/Aim. Chronic venous ulcer (CVU), a disease of high incidence, is one of the most serious chronic venous insufficiency complications. It has been estimated that there are 1%-2% of adults with CVU deriving a high social significance. The aim of this study was to, using the clinical experience, determine the influence of subcutaneous paratibial fasciotomy (SPF) on the course and the treatment outcome of CVU. Methods. From February 2006 to September 2009 SPF was applied in a group of 43 patients treated for CVU along with other standard methods of treatment, and its influence on the course of ulcus cruris was followed up regarding the control group of another 43 patients treated with standard methods with no paratibial fasciotomy. Results. In the group of patients treated with SPF there was a significantly better clinical course of ulcus cruris closing as compared with the group of patients in which this method was not applied. In the group with paratibial fasaciotomy there was no Thiersch skin transplant rejection recorded nor ulcus recurrence within a 6-month after-surgery period, while in the control group there was Thiersch skeen transplant rejection in 11 patients, and ulcus recurrence in 9 patients within the same period. Conclusion. SPF is a useful method with a favorable influence on better clinical course of ulcus cruris closing, reducing recurrence rate and improving local microcirculation in the affected region. Operation act itself is safe, requires no specific equipment nor special training of the team of surgeons, thus being applicable to the majority of patients with ulcus cruris indicated for surgery.

scholarly journals MODERN EFFECTIVE TREATMENT OF BRAIN METASTASES OF SKIN MELANOMA. THE EXAMPLE OF CLINICAL OBSERVATION

2021 ◽  
Vol 20 (2) ◽  
pp. 53-60
Author(s):  
M. I. Kurzhupov ◽  
A. V. Shabunin ◽  
K. S. Titov ◽  
E. L. Slobina ◽  
D. N. Grekov
Keyword(s):  
Radiation Therapy ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Anticancer Therapy ◽  
Skin Melanoma ◽  
Term Survival ◽  
Modern Methods ◽  
Neurosurgical Treatment ◽  
The Brain ◽  
Methods Of Treatment

Introduction. Melanoma of the skin has the highest potential for metastasis to the brain, ranking 15th in the frequency of occurrence among all malignant tumors – it is in third place in the incidence of intracerebral metastases. Modern methods of treatment of metastases of skin melanoma to the brain include neurosurgical treatment, radiation therapy and radiosurgery, antitumor drug therapy, including targeted therapy, immunotherapy and chemotherapy. The article discusses the indications for different methods of treatment, provides data on patient survival when using these methods of treatment alone or in combination. Additionally, a clinical case of long-term survival of a patient with skin melanoma with progression in the form of extra- and intracranial metastasis is discussed.Purpose. Evaluation of the result of using modern methods of antitumor treatment in real clinical practice in a patient with skin melanoma metastases in the brain. Materials and methods. On a clinical example, a possible sequence of an individual approach to the treatment of a patient with extracranial and intracerebral metastases of skin melanoma based on modern methods of treatment and examination is considered.Results. The use of modern methods of anticancer therapy has increased the overall survival and disease-free survival of patients with metastases of skin melanoma to the brain and reduces the need for neurosurgical interventions. As a confirmation of this, the life expectancy of the patient after the progression of skin melanoma in the form of metastases to the brain against the background of all the antitumor treatment carried out to date was 5.5 years, while neurosurgical treatment was not carried out at the request of the patient, although it was shown, but were used the possibilities of modern anticancer therapy, including sequential radiation therapy, targeted therapy and immunotherapy.Conclusion. Modern methods of anticancer therapy can significantly increase the survival rate of patients with melanoma brain metastases and individualize the treatment plan.

Skin wounds’ healing basic problems and the use of skin substitutes

2015 ◽  
Vol 6 (2) ◽  
pp. 85-95 ◽  
Author(s):  
Mariya Valer’yevna Konstantinova ◽  
Nikolay Valentinovich Khaytsev ◽  
Aleftina Alekseevna Kravtsova ◽  
Lev Dmitrievich Balashov
Keyword(s):  
Wound Healing ◽  
Mast Cells ◽  
Adult Stem Cells ◽  
Healing Process ◽  
Wound Healing Process ◽  
Skin Wounds ◽  
Skin Substitutes ◽  
Standard Methods ◽  
Heterogenous Group ◽  
Methods Of Treatment

Kin substitutes present a heterogenous group of substances that aid in temporary or permanent covering of wounds of various types. Although they can not replace surgical debridement or standard methods of treatment they proffer an alternative to standard methods of treatment whenever the latter are ineffective. Skin substitutes require less wound vascularization, they increase the wound’s cutaneous component, decrease or eliminate inhibitory factors, decrease inflammatory process and grant quick and safe wound closing. Mast cells besides regulating vascular reactions in trauma zone also boost immune, defensive and reparative processes in the wound. Stimulatory influence of mast cells upon fibrosis depend on activation of fibroblasts rather than direct collagen production by mast cells. Attention is focused at studies of autologous adult stem-cells’ stimulation in various organs and tissues as well as at intercellular matrix (ICM). ICM besides being cells’ fastening substrate also controls proliferation, differentiation, migration, apoptosis cells’ functions. Collagen, fibronectin, laminin, proteoglycanes, cytokines and chemokynes are important ICM components. Microcirculation plays a substantial role in wound healing process. Cultivated fibroblasts due to their ability for long-term synthesis of ICM components can effectively correct wound healing process. Allogenic fibroblasts can be successfully used as skin substitutes’ components in the treatment of skin wounds and burns. Unlike autologous fibroblasts the allogenic cells may be obtained in advance and freeze-stored in large quantities.

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