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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5609-5609
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5609-5609
    Abstract: Integrative cancer treatment employing natural products (NPs) in conjunction with conventional therapeutic modalities (Tx) is attractive for tumors that are difficult to control clinically. In this context, pluripotent activities of NPs have the potential of affecting multiple processes relevant to cancer growth. Unfortunately, there is little empiric evidence to elucidate clinically useful effects of NPs making it difficult to optimize Tx regimens. This challenge justifies translational studies to characterize NP effects on processes relevant to tumor control. In the current study, we assessed the action of Resveratrol (RV), a phytoalexin present in the skin of red grapes on the sensitivity of human tumors to proliferation inhibition and antitumor immunity. Proliferation was assessed with MTS assay; immune-mediated lysis with 51Chromium release assay; and gene expression with real time PCR. Using the following ATCC cell lines: malignant melanoma (MM); renal (RC); ovarian (OC); non-small cell lung (NSCLC); pancreatic (PC); breast (BC); and bladder (BLC) cancer, significant dose-dependent proliferation inhibition (paired, 2-tail t tests) in RV-treated cells was demonstrated for all tumors with rank order of sensitivity being: MM & gt; RC & gt; OC & gt; NSCLC & gt; BC & gt; BLC & gt; PC. Significant inhibition (p & lt; 0.05) was also observed with tumor cells from surgical specimens from patients with colon, RC, PC, and OC. The substantial proliferation inhibitory effects of RV on MM ( & gt; 80% at 10μg/mL; p = 0.005) and RC ( & gt; 65% at 10μg/mL; p = 0.02) was associated with significant chanages in quantitative expression of various pro and anti-apoptotic regulatory genes. For example, RV-treated MM showed & gt; 8 fold down-regulation of anti-apoptotic BCL2 in association with & gt; 13 fold increase in the death associated kinase, DPK1 and RV-treated RC showed 2-3 fold up-regulation of caspases 1, 5, 7, 10, and 14. Moreover, these studies also revealed significantly increased (2-4 fold) expression of different TNF and TRAIL-related death receptors in RV-treated RC and MM cells. Subsequently, testing the effects of RV-pretreated RC and MM to different forms of antitumor immunity showed: 1)RV pre-treated RC are significantly more sensitive to lysis by IL2-activated human lymphocytes compared to control cells (270 vs 121 lytic units respectively, p=0.04); and, 2) proliferation of MM is inhibited significantly (p & lt;0.05) in an additive fashion by the combination of RV + rTNF or RV + rTRAIL. This study demonstrates that RV can favorably modulate tumor cell proliferation and sensitivity to tumor immune mechanisms in some of the most difficult to treat human cancer histologies. These sorts of studies should facilitate development of integrative treatment modalities to exploit the pluripotent activities of NPs such as RV in specific oncologic settings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5609.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5610-5610
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5610-5610
    Abstract: A substantial challenge in the practice of integrative cancer treatment is to identify active combinations of natural products (NPs) that can collaborate with conventional treatment modalities to achieve enhanced tumor control. This approach is especially attractive for tumors that are inherently chemoresistant or become chemoresistant as a consequence of multidrug resistance. But it has been difficult to prove efficacy of combining NPs with conventional treatment such as chemotherapy due in large part to the challenges inherent in conducting controlled clinical trials with combination regimens. These challenges provide a rationale for translational research studies to characterize effects of NPs on tumor processes relevant to chemoresistance. The current study investigated the activity of Epigallocatechin 3-gallate (EGCG), the principal polyphenol from green tea extract to modulate tumor proliferation and sensitivity to antitumor immunity in human ovarian cancer cells. Tumor proliferation was assessed with a standard MTS assay using the ATCC cell line, OvCar 3 as well as single cell suspensions prepared from human ovarian cancer surgical specimens. Sensitivity to IL2-activated human lymphocytes was assessed with a standard, 4 hr 51Chromium-release assay. EGCG produced a dose-dependent inhhibition of proliferation of the OvCar 3 cell line ranging from & lt;5% (10 ug/mL) through 33% (30 ug/mL). Notably, these concentrations of EGCG are all achievable pharmacologically with a dose of 8, 200 mg capsules daily. Dose dependent inhibition of proliferation was also observed with cells from human ovarian cancer specimens with inhhibition ranging from 10.5% (5 ug/mL) to as much as 54% (25 ug/mL). The effects of EGCG were found to collaborate with pharmacologically achievable concentrations of both cisplatinum (Pt; 500 ng/mL) and gemcitabine (Gz; 10 ng/mL). Thus, 24%, 21% and 60% inhibition of OvCar 3 cells was observed with Pt, EGCG and Pt+EGCG respectively. The corresponding values were 30%, 34%, and 50% inhibition for Gz, EGCG, and Gz+EGCG. Additional effects of EGCG on OvCar 3 were shown in studies using EGCG pre-treatment of target cells prior to testing sensitivity to lysis by IL2-activated human lymphocytes. The results showed that EGCG pretreatment, in doses that did not reduce cell number or inhibit prolliferation over 72 hrs rendered the cells 53% more sensitive to lysis in the 51Chromium-release assay. These results demonstrate direct effects of the principal polyphenol of green tea extract on both the proliferative and immunologic sensitivitiy of human ovarian cancer cells. That these effects can collaborate with chemotherapeutic agents commonly used in the treatment of ovarian cancer patients suggests that combination regimens of this NP with cancer chemotherapy may be valuable in patients for both adjuvant therapy and for maintenance of remission. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5610.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3515-3515
    Abstract: Maitake (Grifola frondosa) has been recognized by naturopathic physicians as a medicinal mushroom capable of immune support. Maitake D-Fraction (MDF), a component of the maitake mushroom isolated during hot-water extraction, is rich in α-Glucans and commonly prescribed as a dietary supplement. Because MDF is widely available and easily tolerated, it is highly desirable for the cancer patient looking for immune support via natural products. Previous research has suggested that a dietary MDF regimen can enhance immune function in humans. However, studies to investigate the capacity of MDF to increase tumor immunity are lacking. This study was designed to investigate whether human peripheral blood mononuclear cells (PBMC) treated with MDF develop increased cytolytic capacity against human tumor cells. Cytolysis mediated by MDF-activated PBMC was compared to that of naïve PBMC (media control) and PBMC that were treated with interleukin-2 (IL-2). Immune mediated tumor cytolysis was assessed used a standard Chromium-Release Assay and expressed as number of lytic units (LU)/10^7 effector cells. Target cells for the assays included the PANC1 pancreatic cancer cell line (PA) purchased from ATCC, and single cell suspensions created from peritoneal carcinomatosis (PC) and renal cell carcinoma (RC) tumors resected from patients. Against the PA cells, the LU observed were 16.9 (media control), 12.9 (1ug/ml MDF), 23.8 (10ug/ml MDF) and 28.9 (100ug/ml MDF). The corresponding LU values against PC cells were 7.6, –13.4, –14.2, and –12.1, respectively, and against RC cells 12.3, 2.7, 2.0, and 8.2, respectively. Predictably, PBMC stimulated with an optimally activating dose of IL2 (200U/ml) exhibited a marked increase in LU against all target cells. Nevertheless, when PBMC were stimulated concurrently with both IL-2 and MDF activation was increased further. Thus, LU against PA target cells were 73.0 for PBMC treated with IL-2 alone, and 110.6 for PBMC treated with IL-2 plus 100ug/ml MDF. The corresponding LU values against PC target cells were 37.1 (IL-2 alone), and 66.4 (IL-2 plus 100ug/ml MDF) and against RC target were 94.0 (IL-2 alone) and 110.7 (IL-2 plus 100ug/ml MDF). This study shows that MDF has the capacity to increase the lytic activity produced by an optimally activating dose of IL-2, eliciting greater killing of a variety of human cancer cells than what can be achieved with IL2 alone. It is reasonable to assume that MDF can elicit a similar effect at lower doses of IL-2. Given the toxicity of IL-2 observed in humans, the potential to elicit the desired immune stimulation by combining lower doses of IL-2 with MDF becomes highly desirable. Future clinical trials should be designed to investigate the ability of MDF to elicit optimal immune stimulation with more tolerable doses and schedules of IL-2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3515. doi:1538-7445.AM2012-3515
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 1993
    In:  The American Journal of Surgery Vol. 166, No. 4 ( 1993-10), p. 350-352
    In: The American Journal of Surgery, Elsevier BV, Vol. 166, No. 4 ( 1993-10), p. 350-352
    Type of Medium: Online Resource
    ISSN: 0002-9610
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1993
    detail.hit.zdb_id: 2003374-6
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2000
    In:  The American Journal of Surgery Vol. 180, No. 4 ( 2000-10), p. 284-287
    In: The American Journal of Surgery, Elsevier BV, Vol. 180, No. 4 ( 2000-10), p. 284-287
    Type of Medium: Online Resource
    ISSN: 0002-9610
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2000
    detail.hit.zdb_id: 2003374-6
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  • 6
    Online Resource
    Online Resource
    Elsevier BV ; 1997
    In:  The American Journal of Surgery Vol. 174, No. 4 ( 1997-10), p. 386-
    In: The American Journal of Surgery, Elsevier BV, Vol. 174, No. 4 ( 1997-10), p. 386-
    Type of Medium: Online Resource
    ISSN: 0002-9610
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1997
    detail.hit.zdb_id: 2003374-6
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  • 7
    In: APMIS, Wiley, Vol. 96, No. 7-12 ( 1988-07), p. 1129-1139
    Abstract: Eighty colon carcinomas reflecting the histologic spectrum were studied immunohistochemically; their epithelial characteristics had been established by demonstrating cytokeratin polypeptides. Paraffin sections were immunostained with monoclonal antibody (Mab) A‐80 that recognizes a mucin‐like glycoprotein related to exocrine differentiation. Sequential sections were immunostained with neuroendocrine (NE) differentiation antibodies: NSE, human chromogranin A, serotonin, somatostatin, substance P and VIP. Twenty‐one/80 carcinomas immunoreacted exclusively with Mab A‐80; these included adenocarcinomas with variably defined glands, colloid, “solid”, and linitits plastica carcinomas. Eleven/80 carcinomas immunoreacted only with antibodies to NE markers. Twenty‐nine/80 carcinomas of histologically variable patterns expressed both exocrine and NE antigens. A notable group of 19 adenocarcinomas immunostaining with Mab A‐870 included a minority NE cell subpopulation. We tentatively conclude that given a limited battery of immunoprobes, colon carinomas comprise 4 groups: 1) pure exocrine carcinomas, 2) pure NE carcinomas, 3) mixed exocrine and NE carcinomas, and 4) exocrine carcinomas with occasional NE cells. Thus, phenotypically mixed exocrine and NE carcinomas comprise the largest group while the second largest group exhibited exclusively features of exocrine phenotype. Preliminary clinical correlative data indicate that pure NE colon carcinomas behave more aggressively than their exocrine counterparts; moreover, colon carcinomas containing a NE subpopulation, even if small, also seem to behave worse than their counterparts without an NE subpopulation.
    Type of Medium: Online Resource
    ISSN: 0903-4641 , 1600-0463
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 1988
    detail.hit.zdb_id: 2098213-6
    SSG: 12
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  • 8
    In: APMIS, Wiley, Vol. 97, No. 7-12 ( 1989-07), p. 1053-1067
    Abstract: We studied by immunocytochemistry 573 tissue and 106 cytologic samples of human tumors, non‐neoplastic proliferative lesions and normal tissues with the monoclonal antibody (Mab) A‐80 that recognizes a mucinous glycoprotein from the colon carcinoma cell line LS‐174T. The spectrum of benign and malignant breast lesions was studied as were epithelial tumors of the colon, stomach, pancreas, lung, salivary glands, thyroid, prostate, kidney, endometrium, skin and mesothelium; non‐epithelial tumors included lymphomas, melanomas, gliomas, meningiomas, and sarcomas of soft tissue and bone. With a single exception, breast carcinomas regardless of histologic type were reactive while few fibroadenomas stained weakly and focally. In fibrocystic disease, the presence and intensity of the reactivity paralleled the severity of the epithelial proliferation, e.g. staining was strong in foci of severe or atypical hyperplasia, borderline lesions and carcinomas in situ; apocrine metaplasia stained often but less strongly. Barrett's mucosa, colonic polyps and most gastric and colonic carcinomas stained regardless of glandular features while small cell neuroendocrine carcinomas did not. Adenocarcinomas of the pancreas and lung, and a subset of large cell lung carcinomas reacted whereas neuroendocrine carcinomas of those sites did not. Carcinomas of endometrium, ovary and prostate reacted variably whereas thyroid and renal carcinomas and mesotheliomas were either negative or weakly reactive despite the presence of glands. Lymphomas, skin adnexal tumors, nevi, schwannomas, melanomas, gliomas and sarcomas generally did not react but occasional A‐80‐positive cells were seen in rare sarcomas and meningiomas. Immunostaining patterns in cytologic specimens were similar to the aforementioned. We conclude that Mab A‐80 is an excellent marker for breast carcinomas, and for certain proliferative forms of fibrocystic disease that may precede or be associated with carcinomatous transformation. In colonic, pulmonary and gastric carcinomas, staining with Mab A‐80 revealed exocrine features regardless of the absence of glands whereas in renal and thyroid carcinomas and in mesotheliomas staining was focal and weak or absent irrespective of glandular features. We suggest that Mab A‐80 is a very promising immunolabel for select exocrine carcinomas, and for some of the dysplasias that may precede their development; its ease of application on tissue sections and cytologic specimens should broaden its usefulness.
    Type of Medium: Online Resource
    ISSN: 0903-4641 , 1600-0463
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 1989
    detail.hit.zdb_id: 2098213-6
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    American Medical Association (AMA) ; 1996
    In:  Archives of Surgery Vol. 131, No. 6 ( 1996-06-01), p. 651-
    In: Archives of Surgery, American Medical Association (AMA), Vol. 131, No. 6 ( 1996-06-01), p. 651-
    Type of Medium: Online Resource
    ISSN: 0004-0010
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 1996
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  • 10
    Online Resource
    Online Resource
    American Medical Association (AMA) ; 1992
    In:  Archives of Surgery Vol. 127, No. 11 ( 1992-11-01), p. 1282-
    In: Archives of Surgery, American Medical Association (AMA), Vol. 127, No. 11 ( 1992-11-01), p. 1282-
    Type of Medium: Online Resource
    ISSN: 0004-0010
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 1992
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