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  1. Article ; Online: A review of immune therapy in cancer and a question: can thermal therapy increase tumor response?

    Bull, Joan M C

    International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

    2017  Volume 34, Issue 6, Page(s) 840–852

    Abstract: Immune therapy is a successful cancer treatment coming into its own. This is because checkpoint molecules, adoptive specific lymphocyte transfer and chimeric antigen T-cell (CAR-T) therapy are able to induce more durable responses in an increasing number ...

    Abstract Immune therapy is a successful cancer treatment coming into its own. This is because checkpoint molecules, adoptive specific lymphocyte transfer and chimeric antigen T-cell (CAR-T) therapy are able to induce more durable responses in an increasing number of malignancies compared to chemotherapy. In addition, immune therapies are able to treat bulky disease, whereas standard cytotoxic therapies cannot treat large tumour burdens. Checkpoint inhibitor monoclonal antibodies are becoming widely used in the clinic and although more complex, adoptive lymphocyte transfer and CAR-T therapies show promise. We are learning that there are nuances to predicting the successful use of the checkpoint inhibitors as well as to specific-antigen adoptive and CAR-T therapies. We are also newly aware of a here-to-fore unrealised natural force, the status of the microbiome. However, despite better understanding of mechanisms of action of the new immune therapies, the best responses to the new immune therapies remain 20-30%. Likely the best way to improve this somewhat low response rate for patients is to increase the patient's own immune response. Thermal therapy is a way to do this. All forms of thermal therapy, from fever-range systemic thermal therapy, to high-temperature HIFU and even cryotherapy improve the immune response pre-clinically. It is time to test the immune therapies with thermal therapy in vivo to test for optimal timing of the combinations that will best enhance tumour response and then to begin to test the immune therapies with thermal therapy in the clinic as soon as possible.
    MeSH term(s) Humans ; Immunotherapy/methods ; Neoplasms/therapy
    Language English
    Publishing date 2017-11-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 632526-9
    ISSN 1464-5157 ; 0265-6736
    ISSN (online) 1464-5157
    ISSN 0265-6736
    DOI 10.1080/02656736.2017.1387938
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer.

    Sonpavde, Guru / McMannis, John D / Bai, Yu / Seethammagari, Mamatha R / Bull, Joan M C / Hawkins, Victoria / Dancsak, Theresa K / Lapteva, Natasha / Levitt, Jonathan M / Moseley, Annemarie / Spencer, David M / Slawin, Kevin M

    Cancer immunology, immunotherapy : CII

    2017  Volume 66, Issue 10, Page(s) 1345–1357

    Abstract: This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected ...

    Abstract This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation. Eighteen men with progressive mCRPC following ≤1 prior chemotherapy regimen were enrolled to evaluate three doses of BPX101 (4 × 10
    MeSH term(s) Aged ; CD40 Antigens/metabolism ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Cohort Studies ; Dendritic Cells/immunology ; Humans ; Male ; Prostatic Neoplasms/immunology
    Chemical Substances CD40 Antigens ; Cancer Vaccines
    Language English
    Publishing date 2017-06-12
    Publishing country Germany
    Document type Clinical Trial, Phase I ; Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-017-2027-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Fever-range whole body thermotherapy combined with oxaliplatin: a curative regimen in a pre-clinical breast cancer model.

    Rowe, R Wanda / Strebel, Frederick R / Proett, Jesse M / Deng, Wanleng / Chan, Diana / He, Guangan / Siddik, Zahid / Bull, Joan M C

    International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

    2010  Volume 26, Issue 6, Page(s) 565–576

    Abstract: Purpose: Studies were conducted to test whether fever-range whole body thermal therapy would boost the efficacy of oxaliplatin chemotherapy without substantial toxicity.: Materials and methods: The effect of mild heat (40 degrees C) on oxaliplatin ... ...

    Abstract Purpose: Studies were conducted to test whether fever-range whole body thermal therapy would boost the efficacy of oxaliplatin chemotherapy without substantial toxicity.
    Materials and methods: The effect of mild heat (40 degrees C) on oxaliplatin cytotoxicity, cellular uptake, and platinum-DNA adduct formation was studied in vitro using the MTLn3 tumour cell line. In vivo oxaliplatin was administered at various doses and times before, during and after fever-range thermal therapy (6 h at 40 degrees C) to rats bearing an MTLn3 mammary adenocarcinoma. Tumour growth, survival, and toxicity were measured to determine treatment outcome.
    Results: Heating halved the oxaliplatin IC-50 dose for MTLn3 cells. Cellular uptake of platinum and platinum adducts increased by 34% and 36%, respectively, with heat. In vivo, 50% of all rats given 10 mg/kg oxaliplatin 24 h before thermal therapy were completely immunologically cured, while a further 11% regressed their primary tumour but ultimately succumbed to metastases, and 17% experienced a limited response with increased survival. The curative response occurred only in a narrow range of doses, with most cures at 10 mg/kg. Thermochemotherapy-treated, but uncured, animals had delayed incidence and slowed growth of metastases. Anti-tumour efficacy was greatest, and toxicity was least, when oxaliplatin was administered 12 or 24 h before fever-range whole body thermal therapy.
    Conclusions: When properly dosed and scheduled, oxaliplatin thermochemotherapy achieved permanent eradication of all primary and metastatic tumours in 50% of animals, seemingly through an immune response. Successful clinical translation of this protocol would yield hitherto unseen cures and substantial improvement in quality of life.
    MeSH term(s) Adenocarcinoma/metabolism ; Adenocarcinoma/therapy ; Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/metabolism ; Breast Neoplasms/therapy ; Cell Line, Tumor ; Combined Modality Therapy ; DNA Adducts/metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Fever/physiopathology ; Hyperthermia, Induced/methods ; Organoplatinum Compounds/administration & dosage ; Organoplatinum Compounds/therapeutic use ; Oxaliplatin ; Platinum/metabolism ; Rats ; Rats, Inbred F344 ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; DNA Adducts ; Organoplatinum Compounds ; Oxaliplatin (04ZR38536J) ; Platinum (49DFR088MY)
    Language English
    Publishing date 2010-08-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632526-9
    ISSN 1464-5157 ; 0265-6736
    ISSN (online) 1464-5157
    ISSN 0265-6736
    DOI 10.3109/02656736.2010.483635
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The natural progression of microvasculature in primary tumor and lymph node metastases in a breast carcinoma model: relationship between microvessel density, vascular endothelial growth factor expression, and metastatic invasion.

    Rowe, R Wanda / Tomoda, Masaaki / Strebel, Frederick R / Jenkins, Gaye N / Stephens, L Clifton / Bull, Joan M C

    Cancer biology & therapy

    2004  Volume 3, Issue 4, Page(s) 408–414

    Abstract: The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and ... ...

    Abstract The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and metastatic axillary (ALN) and inguinal lymph node (ILN) tumors over 5-6 tumor doublings. Excised tumors were examined for (i) MVD assessed by immunostaining with anti-CD31 antibody, (ii) VEGF expression assessed by immunostaining with anti-VEGF antibody, and (iii) histopathologic extent of metastatic lymph node invasion. MVD and VEGF scores rose asymptotically with increasing tumor weight in both primary and metastatic tumors. The MVD saturation level was significantly greater for primary tumors (MVD = 22) than for ALNs or ILNs (MVD = 14). Maximal VEGF score was not statistically different between the three kinds of tumors, however the rate of rise in VEGF expression was different. Near-maximal VEGF expression occurred early in tumor growth, preceding microvessel development. Both MVD and VEGF expression in lymph nodes were proportional to the pathology score characterizing increasing metastatic invasion. LNMs limited to the subcapsular sinus had the lowest MVD, indicating an ability to survive without significant vasculature. These findings underscore the differences in angiogenesis between primary tumors and LNMs and have implications for therapy of metastatic cancer.
    MeSH term(s) Animals ; Carcinoma/blood supply ; Carcinoma/pathology ; Female ; Immunoassay ; Lymphatic Metastasis/physiopathology ; Mammary Neoplasms, Animal/blood supply ; Mammary Neoplasms, Animal/pathology ; Microcirculation ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Rats ; Rats, Inbred F344 ; Vascular Endothelial Growth Factor A/biosynthesis
    Chemical Substances Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2004-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2146305-0
    ISSN 1538-4047
    ISSN 1538-4047
    DOI 10.4161/cbt.3.4.779
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-alpha: a description of a phase I-II protocol.

    Bull, Joan M C / Scott, Glenna L / Strebel, Frederick R / Nagle, Verne L / Oliver, Dwight / Redwine, Michael / Rowe, R Wanda / Ahn, Chul W / Koch, Steven M

    International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

    2008  Volume 24, Issue 8, Page(s) 649–662

    Abstract: Purpose: The purpose of the Phase I component of this study was to find the maximally tolerated dose (MTD) of cisplatin administered within a regimen of fever-range whole body thermal therapy (FR-WB-TT), cisplatin, gemcitabine, and low-dose interferon- ... ...

    Abstract Purpose: The purpose of the Phase I component of this study was to find the maximally tolerated dose (MTD) of cisplatin administered within a regimen of fever-range whole body thermal therapy (FR-WB-TT), cisplatin, gemcitabine, and low-dose interferon-alpha (IFN-alpha). The Phase II component aimed to assess which cancer diagnoses responded to the regimen, the response rate, and response duration.
    Materials and methods: The protocol design derived from a schedule-optimized preclinical regimen. Drugs were administered together, and also with thermal therapy in a schedule that optimized the therapeutic index. Eligible patients were those with therapy-resistant, metastatic or advanced solid malignancies. Beginning at 40 mg/m(2), the cisplatin dose was escalated by 10 mg/m(2) to the maximally tolerated dose (MTD) in successive cohorts of 3 patients. A treatment cycle consisted of cisplatin on day one, followed by thermal therapy and simultaneous gemcitabine 36 hours later; then a second dose of gemcitabine one week later; and daily IFN- alpha.
    Results: Thirty-seven patients were treated on protocol. The MTD of cisplatin in the thermochemotherapy regimen was established to be 60 mg/m(2). The dose limiting toxicities (DLT) were peripheral neuropathy and ototoxicity. Complete and partial responses combined were 43%. The therapy improved the quality of life of responding patients.
    Conclusion: The protocol was well tolerated and was associated with antitumor activity in patients with a variety of advanced metastatic solid tumors. Tumor response occurred with the thermochemotherapy treatment despite treating malignancies that had progressed on the same chemotherapy drugs administered as standard treatment. Notably, good responses were observed in patients with high-grade neuroendocrine and pancreas cancers. This regimen will be tested in a phase II study.
    MeSH term(s) Adult ; Aged ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Cisplatin/therapeutic use ; Combined Modality Therapy ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/therapeutic use ; Disease Progression ; Drug Administration Schedule ; Female ; Humans ; Hyperthermia, Induced ; Interferon-alpha/therapeutic use ; Kaplan-Meier Estimate ; Male ; Maximum Tolerated Dose ; Middle Aged ; Neoplasms/therapy ; Quality of Life
    Chemical Substances Antimetabolites, Antineoplastic ; Antineoplastic Agents ; Interferon-alpha ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2008-12
    Publishing country England
    Document type Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632526-9
    ISSN 1464-5157 ; 0265-6736
    ISSN (online) 1464-5157
    ISSN 0265-6736
    DOI 10.1080/02656730802104740
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: In regard to Vasanathan et al. (Int J Radiat Oncol Biol Phys 2005;61:145-153).

    Jones, Ellen L / Prosnitz, Leonard R / Dewhirst, Mark W / Vujaskovic, Zeljko / Samulski, Thaddeus V / Oleson, James R / Yu, Daohi / Myerson, Robert J / Moros, Eduardo G / Hurwitz, Mark D / Bull, Joan M C

    International journal of radiation oncology, biology, physics

    2005  Volume 63, Issue 2, Page(s) 644

    MeSH term(s) Combined Modality Therapy ; Female ; Humans ; Hyperthermia, Induced/methods ; Hyperthermia, Induced/standards ; Radiotherapy/standards ; Radiotherapy Dosage ; Uterine Cervical Neoplasms/radiotherapy ; Uterine Cervical Neoplasms/therapy
    Language English
    Publishing date 2005-10-01
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2005.06.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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