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  1. Article: Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles.

    Miroshnychenko, Daria / Miti, Tatiana / Kumar, Pragya / Miller, Anna / Laurie, Mark / Giraldo, Nathalia / Bui, Marilyn M / Altrock, Philipp M / Basanta, David / Marusyk, Andriy

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this ... ...

    Abstract The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. Our
    Language English
    Publishing date 2023-07-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.07.527543
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles.

    Miroshnychenko, Daria / Miti, Tatiana / Kumar, Pragya / Miller, Anna / Laurie, Mark / Giraldo, Nathalia / Bui, Marilyn M / Altrock, Philipp M / Basanta, David / Marusyk, Andriy

    Cancer research

    2023  Volume 83, Issue 22, Page(s) 3681–3692

    Abstract: The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this ... ...

    Abstract The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity induced by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. In vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, fibroblast-produced secreted factors stimulated treatment-independent enhancement of tumor cell proliferation. Spatial analyses indicated that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. These observations suggested an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate this hypothesis, a spatial agent-based model of stroma impact on proliferation/death dynamics was developed that was quantitatively parameterized using inferences from histologic analyses and experimental studies. The model demonstrated that the observed enhancement of tumor cell proliferation within stroma-proximal niches could enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, this study supports the existence of an indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes.
    Significance: Integration of experimental research with mathematical modeling reveals an indirect microenvironmental chemoresistance mechanism by which stromal cells stimulate breast cancer cell proliferation and highlights the importance of consideration of proliferation/death dynamics. See related commentary by Wall and Echeverria, p. 3667.
    MeSH term(s) Humans ; Drug Resistance, Neoplasm ; Triple Negative Breast Neoplasms/pathology ; Cell Proliferation ; Fibroblasts/metabolism ; Stromal Cells/metabolism ; Cell Line, Tumor
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-23-0398
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Two sisters in the same dress

    Bermingham Eldredge / Jiggins Chris D / Salazar Camilo / Giraldo Nathalia / Linares Mauricio

    BMC Evolutionary Biology, Vol 8, Iss 1, p

    Heliconius cryptic species

    2008  Volume 324

    Abstract: Abstract Background Sister species divergence and reproductive isolation commonly results from ecological adaptation. In mimetic Heliconius butterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly ... ...

    Abstract Abstract Background Sister species divergence and reproductive isolation commonly results from ecological adaptation. In mimetic Heliconius butterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly correlated with speciation. Closely related mimetic species are therefore not expected, as they should lack several important sources of reproductive isolation. Results Here we present phenotypic, behavioral and genetic evidence for the coexistence of two sympatric 'cryptic' species near Florencia in the eastern Andes of Colombia that share the same orange rayed colour pattern. These represent H. melpomene malleti and a novel taxon in the H. cydno group, here designated as novel race of Heliconius timareta , Heliconius timareta florencia . No-choice mating experiments show that these sympatric forms have strong assortative mating (≈96%) despite great similarity in colour pattern, implying enhanced divergence in pheromonal signals. Conclusion We hypothesize that these species might have resulted from recent convergence in colour pattern, perhaps facilitated by hybrid introgression of wing pattern genes.
    Keywords Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Evolution ; QH359-425
    Subject code 590
    Language English
    Publishing date 2008-11-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Two sisters in the same dress: Heliconius cryptic species.

    Giraldo, Nathalia / Salazar, Camilo / Jiggins, Chris D / Bermingham, Eldredge / Linares, Mauricio

    BMC evolutionary biology

    2008  Volume 8, Page(s) 324

    Abstract: Background: Sister species divergence and reproductive isolation commonly results from ecological adaptation. In mimetic Heliconius butterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly ... ...

    Abstract Background: Sister species divergence and reproductive isolation commonly results from ecological adaptation. In mimetic Heliconius butterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly correlated with speciation. Closely related mimetic species are therefore not expected, as they should lack several important sources of reproductive isolation.
    Results: Here we present phenotypic, behavioral and genetic evidence for the coexistence of two sympatric 'cryptic' species near Florencia in the eastern Andes of Colombia that share the same orange rayed colour pattern. These represent H. melpomene malleti and a novel taxon in the H. cydno group, here designated as novel race of Heliconius timareta, Heliconius timareta florencia. No-choice mating experiments show that these sympatric forms have strong assortative mating ( approximately 96%) despite great similarity in colour pattern, implying enhanced divergence in pheromonal signals.
    Conclusion: We hypothesize that these species might have resulted from recent convergence in colour pattern, perhaps facilitated by hybrid introgression of wing pattern genes.
    MeSH term(s) Animals ; Butterflies/classification ; Butterflies/genetics ; Butterflies/physiology ; Colombia ; Color ; DNA, Mitochondrial/genetics ; Female ; Genetic Speciation ; Male ; Microsatellite Repeats ; Phenotype ; Phylogeny ; Reproduction ; Sexual Behavior, Animal
    Chemical Substances DNA, Mitochondrial
    Language English
    Publishing date 2008-11-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-2148
    ISSN (online) 1471-2148
    DOI 10.1186/1471-2148-8-324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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