Correlation of clinical data with fallopian tube specimen immune cells and tissue culture capacity

Ramraj, Satish Kumar; Smith, Katie; Janakiram, Naveena B.; Toal, Coralee; Raman, Ankita; Benbrook, Doris M.

doi:10.1016/j.tice.2018.04.001

Cited by 6 publications

(2 citation statements)

References 27 publications

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“…In prostate cancer, SASP antiproliferative activity toward the cells surrounding an aging cell was observed only in healthy cells or aging cells with minor mutations and, importantly, had no such effect on tumor cells [175]. The suppressive effect of cellular senescence on systemic inflammation appears to be confirmed indirectly by an increase in release of IL-10 with age [176].…”

Section: Hypoxia-inducible Factor 1 Dependent Cytokinesmentioning

confidence: 97%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: Hypoxia-inducible Factor 1 Dependent Cytokinesmentioning

confidence: 97%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…They define 12 major cell types in healthy uterine tubes, from 4 are immune cells (B lymphocytes, T lymphocytes/NK cells, mast cells and macrophages). Ramraj et al (2018) , in a flow cytometric analysis of immunocompetent cells from dispersed tubal specimens, indicates that the predominant cell type is M1 macrophages (20% of total cells); followed by regulatory T lymphocytes (7%), CD8 cytotoxic T lymphocytes (3%), M2 macrophages (1%), perforin-positive natural killer (NK) cells (0.52%), and granzyme B-positive NK cells (0.13%). The aim of this narrative review is to present a comprehensive overview of the immune cell populations in the wall of human uterine tubes.…”

Section: Introductionmentioning

confidence: 99%

Morphology of the immune cells in the wall of the human uterine tube and their possible impact on reproduction—uterine tube as a possible immune privileged organ

Visnyaiová,

Varga,

Feitscherová

et al. 2024

Front. Cell Dev. Biol.

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The uterine tube, as well as other parts of the upper female reproductive system, is immunologically unique in its requirements for tolerance to allogenic sperm and semi-allogenic embryos, yet responds to an array of sexually transmitted pathogens. To understand this dichotomy, there is a need to understand the functional morphology of immune cells in the wall of the uterine tube. Thus, we reviewed scientific literature regarding immune cells and the human uterine tube by using the scientific databases. The human uterine tube has a diverse population of immunocompetent cells representing both the innate and adaptive immune systems. We describe in detail the possible roles of cells of the mononuclear phagocyte system (macrophages and dendritic cells), T and B lymphocytes, natural killer cells, neutrophils and mast cells in association with the reproductive functions of uterine tubes. We are also discussing about the possible “immune privilege” of the uterine tube, as another mechanism to tolerate sperm and embryo without eliciting an inflammatory immune response. In uterine tube is not present an anatomical blood-tissue barrier between antigens and circulation. However, the immune cells of the uterine tube probably represent a type of “immunological barrier,” which probably includes the uterine tube among the immunologically privileged organs. Understanding how immune cells in the female reproductive tract play roles in reproduction is essential to understand not only the mechanisms of gamete transport and fertilization as well as embryo transport through the uterine tube, but also in improving results from assisted reproduction.

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Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53

Ramraj

Elayapillai

Pelikan

et al. 2020

Intl Journal of Cancer

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Current ovarian cancer maintenance therapy is limited by toxicity and no proven impact on overall survival. To study a maintenance strategy targeted at missense mutant p53, we hypothesized that the release of mutant p53 from mortalin inhibition by the SHetA2 drug combined with reactivation of mutant p53 with the PRIMA‐1MET drug inhibits growth and tumor establishment synergistically in a mutant‐p53 dependent manner. The Cancer Genome Atlas (TCGA) data and serous ovarian tumors were evaluated for TP53 and HSPA9/mortalin status. SHetA2 and PRIMA‐1MET were tested in ovarian cancer cell lines and fallopian tube secretory epithelial cells using isobolograms, fluorescent cytometry, Western blots and ELISAs. Drugs were administered to mice after peritoneal injection of MESOV mutant p53 ovarian cancer cells and prior to tumor establishment, which was evaluated by logistic regression. Fifty‐eight percent of TP53 mutations were missense and there were no mortalin mutations in TCGA high‐grade serous ovarian cancers. Mortalin levels were sequentially increased in serous benign, borderline and carcinoma tumors. SHetA2 caused p53 nuclear and mitochondrial accumulation in cancer, but not in healthy, cells. Endogenous or exogenous mutant p53 increased SHetA2 resistance. PRIMA‐1MET decreased this resistance and interacted synergistically with SHetA2 in mutant and wild type p53‐expressing cell lines in association with elevated reactive oxygen species/ATP ratios. Tumor‐free rates in animals were 0% (controls), 25% (PRIMA1MET), 42% (SHetA2) and 67% (combination). SHetA2 (p = 0.004) and PRIMA1MET (p = 0.048) functioned additively in preventing tumor development with no observed toxicity. These results justify the development of SHetA2 and PRIMA‐1MET alone and in combination for ovarian cancer maintenance therapy.

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Correlation of clinical data with fallopian tube specimen immune cells and tissue culture capacity

Cited by 6 publications

References 27 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Morphology of the immune cells in the wall of the human uterine tube and their possible impact on reproduction—uterine tube as a possible immune privileged organ

Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53

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