Peter Mac Callum Cancer Center

Melbourne, Australia

Peter Mac Callum Cancer Center

Melbourne, Australia

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Mardiana S.,Peter MacCallum Cancer Center | Mardiana S.,University of Melbourne | John L.B.,Peter MacCallum Cancer Center | John L.B.,University of Melbourne | And 26 more authors.
Cancer Research | Year: 2017

Adoptive immunotherapy utilizing chimeric antigen receptor (CAR) T cells has demonstrated high success rates in hematologic cancers, but results against solidmalignancies have been limited to date, due in part to the immunosuppressive tumor microenvironment. Activation of the 4-1BB (CD137) pathway using an agonistic α-4-1BB antibody is known to provide strong costimulatory signals for augmenting and diversifying T-cell responses.Wetherefore hypothesized that a combination of α-4-1BB and CAR T-cell therapy would result in improved antitumor responses. Using a human-Her2 self-antigen mouse model, we report here that α-4- 1BB significantly enhanced CAR T-cell efficacy directed against the Her2 antigen in two different established solid tumor settings. Treatment also increased the expression of IFNg and the proliferation marker Ki67 in tumor-infiltrating CAR T cells when combined with α-4-1BB. Strikingly, α-4-1BB significantly reduced host immunosuppressive cells at the tumor site, including regulatory T cells and myeloid-derived suppressor cells, correlating with an increased therapeutic response. We conclude that α-4-1BB has a multifunctional role for enhancing CAR T-cell responses and that this combination therapy has high translational potential, given current phase I/II clinical trials with α-4-1BB against various types of cancer. © 2017 American Association for Cancer Research.


Mele T.,Oncologia Medica | Mele T.,Breast Unit | Generali D.,Breast Unit | Fox S.,Peter Mac Callum Cancer Center | And 11 more authors.
Breast Cancer Research and Treatment | Year: 2010

Vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor 2 (VEGFR2) are the key factors mediating neo-vascularization. They are often coexpressed in breast cancer. Sex steroids may stimulate angiogenesis via the estrogen receptor (ER) pathway. We investigated to compare the effects of the addition of tamoxifen to epirubicin versus epirubicin alone on VEGF and VEGFR2 expression in breast cancer patients. The expression of VEGF and VEGFR2 was assessed on tissue microarray by immunohistochemistry at baseline conditions and after treatments in the case of 191 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin plus tamoxifen as primary systemic treatment. Epirubicin alone failed to induce changes in VEGF expression (P = 0.54), while the addition of tamoxifen to epirubicin resulted in a significant reduction in VEGF expression (P < 0.001). As a consequence, baseline VEGF had a negative prognostic role in patients who received epirubicin alone but not in patients receiving epirubicin plus tamoxifen (interaction test P < 0.05). VEGFR2 expression increased at residual tumor histology in both treatment arms, with a lesser extent in patients receiving tamoxifen plus epirubicin. Decrease in VEGFR2 expression was significantly associated with response rate (P = 0.02). The addition of tamoxifen to epirubicin resulted in a suppression of a key angiogenic pathway. These data suggest a potential synergism of these two drugs. © Springer Science+Business Media, LLC. 2010.


Haeusler G.M.,Peter Mac Callum Cancer Center | Haeusler G.M.,Monash Childrens Hospital | Sung L.,Hospital for Sick Children | Ammann R.A.,University of Bern | And 2 more authors.
Current Opinion in Infectious Diseases | Year: 2015

Risk stratification is recommended for children with cancer and fever and neutropenia. Further research is required to quantify the overall impact of this approach and to refine exactly which children will benefit from early antibiotic administration as well as modifications to empiric regimens to cover antibiotic-resistant organisms. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Kelleher F.C.,Peter Mac Callum Cancer Center | Kelleher F.C.,St Vincents University Hospital | Viterbo A.,St Vincents University Hospital | Viterbo A.,St Andrea University Hospital
Cancers | Year: 2013

Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term "malignant fibrous histiocytoma" being replaced by "UPS". In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and "not-otherwise-specified" (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1), Peroxisome proliferator- activated receptor γ (PPARγ), Nerve growth factor β (NGF β) and Fibroblast growth factor receptor (FGFR). © 2013 by the authors; licensee MDPI, Basel, Switzerland.


Smart P.J.,Peter Mac Callum Cancer Center | Smart P.J.,General Surgery and Gastroenterology Clinical Institute | Burbury K.L.,Peter Mac Callum Cancer Center | Lynch A.C.,Peter Mac Callum Cancer Center | And 2 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2014

Thromboembolism a common, costly, and morbid complication that is also associated with decreased survival in cancer patients. The risk of thromboembolism in cancer patients is underappreciated. In addition to symptomatic deep venous thrombosis and pulmonary embolism, asymptomatic and arterial thromboembolic events are important consideration in ambulatory cancer patients receiving neoadjuvant chemoradiotherapy (nCRT). No specific randomized trial examining thromboprophylaxis (TP) during nCRT for gastrointestinal cancer has been performed, and none is accruing. Most guidelines currently recommend against TP in ambulatory cancer patients due to a lack of data rather than proof of harm or lack of efficacy. It is clear that robust data are urgently required, and that treatment with nCRT in patients with gastrointestinal malignancy is not an indication for routine pharmacological TP at the present time. Copyright © 2012 by Lippincott Williams & Wilkins.


Kelleher F.C.,St Vincents University Hospital | Kelleher F.C.,Peter Mac Callum Cancer Center | McDermott R.,St Vincents University Hospital | McDermott R.,Adelaide and Meath Hospital
Vitamins and Hormones | Year: 2012

To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. A PubMed search from 2000 to 2010 and literature-based references were sourced. It was found that in 2009 a genetic analysis of pancreatic cancers discovered that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Second, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) have shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Third, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compressed the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourth, it has been found that ligand-dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA + immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA + cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment.In conclusion, aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer. © 2012 Elsevier Inc.


Kinnane N.A.,Peter Mac Callum Cancer Center | Milne D.J.,Peter Mac Callum Cancer Center
Supportive Care in Cancer | Year: 2010

Background The Internet is an expanding source of information and support for cancer patients and their families. Studies mostly report patient Internet use. Little is known about how carers (families/informal caregivers/friends) use the Internet and what they find useful. Aim The aim of this paper was to review the literature on the role of the Internet in supporting and informing carers of people with cancer. Materials and methods: Findings are based on a review of published studies identified from 1996-2009 Ovid MED-LINE, CINAHL, EMBASE and 2002-2009 PsycINFO, Cochrane database and Google Scholar. Key search words used were cancer, patient, information, Internet, online, web, support, family, carer, caregiver and friend. Results: One hundred forty-five abstracts were reviewed. Fifty-two articles were retrieved in full text. Twenty of the 52 articles were critically appraised using the appropriate Critical Appraisal Skills Programme tool. All studies retrieved were level IV evidence. Most compared carer and patient Internet use with other cancer information sources or analysed content of postings to web sites. Some reported on patient 'indirect' Internet use through carers. Heterogeneity of results related to different study aims, diversity in study tools, varying sample sizes and differing cancer populations. Broadly, Internet use can be divided into information searching and support group activity. Carers access Internet information to problem solve; however, they report doctors as their most preferred information source. They would like to have e-mail communication with Health Care Professionals to ask questions and clarify information. Participation in online support groups provides information tailored to individual needs and peer support. Implications for practice; The Internet may be a primary or secondary source of information and can be used to access services. Routine assessment of carers' Internet use, prescribing of Internet sites and e-mail communication with carers are possible areas for practice improvement. The current level of evidence is not ideal to influence policy development. Conclusions: Research is required to evaluate carer Internet use in the rapidly changing world of health and technology. Interactive Internet applications developed specifically for carer use have the potential to prepare, inform and support the carer in their ever-expanding health care role. The impact of these services on carer quality of life also requires investigation. © Springer-Verlag 2010.


Lethborg C.,St Vincents Hospital | Brown R.,St Vincents Hospital | Posenelli S.,St Vincents Hospital | Pollerd L.,Peter Mac Callum Cancer Center | And 4 more authors.
Journal of Psychosocial Oncology | Year: 2014

Although the complexity of age combined with a cancer diagnosis can result in unmet supportive care needs there are seldom resources to assess or address such needs for older people with cancer (OPWC). The purpose of this project was to trial a service to improve the care for OPWC through (1) an expanded supportive care screening process and (2) capacity building of subacute ambulatory care services (SACS) staff to increase referrals to community-based rehabilitation. Methods/design: Collaboration between allied health (AH) staff at an inner city general hospital with a large cancer service, a cancer specialist hospital, and a SACS service in Melbourne, Australia, developed an AH geriatric screening assessment (GSA) tool. Parallel to this process training was provided to SACS staff in relation to working with OPWC. Although close to one half (44%) of SACS staff who participated in this program (n = 22) had over 6 years experience, 32% had not worked with OPWC. Prior to training, 81% did not feel confident in their knowledge about working with this cohort. After their training 72% were more confident about normal aging and implications for care of OPWC. Of the 491 patients screened, 80% were older than age 65, however, only 25 resided in the SACS catchment area. More than one third of these did not have clear rehabilitation needs, and the remainder were not referred due to ongoing medical issues. Less than one half of the patients in the catchment area were discussed in a Multi-disciplinary Meeting (MDM) but all were referred to allied health and assessed using the GSA. Although this project did not result in referrals of OPWC to SACS the training program for SACS staff was a success and allied health assessments were improved to include GSA factors. The complexity of care for OPWC was further highlighted through interviews with staff involved with the study. Copyright © 2014 Taylor & Francis Group, LLC.


PubMed | Peter Mac Callum Cancer Center
Type: Journal Article | Journal: Cancers | Year: 2013

Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term malignant fibrous histiocytoma being replaced by UPS. In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and not-otherwise-specified (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1), Peroxisome proliferator-activated receptor (PPAR), Nerve growth factor (NGF ) and Fibroblast growth factor receptor (FGFR).


PubMed | Peter Mac Callum Cancer Center
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2010

The Internet is an expanding source of information and support for cancer patients and their families. Studies mostly report patient Internet use. Little is known about how carers (families/informal caregivers/friends) use the Internet and what they find useful.The aim of this paper was to review the literature on the role of the Internet in supporting and informing carers of people with cancer.Findings are based on a review of published studies identified from 1996-2009 Ovid MEDLINE, CINAHL, EMBASE and 2002-2009 PsycINFO, Cochrane database and Google Scholar. Key search words used were cancer, patient, information, Internet, online, web, support, family, carer, caregiver and friend.One hundred forty-five abstracts were reviewed. Fifty-two articles were retrieved in full text. Twenty of the 52 articles were critically appraised using the appropriate Critical Appraisal Skills Programme tool. All studies retrieved were level IV evidence. Most compared carer and patient Internet use with other cancer information sources or analysed content of postings to web sites. Some reported on patient indirect Internet use through carers. Heterogeneity of results related to different study aims, diversity in study tools, varying sample sizes and differing cancer populations. Broadly, Internet use can be divided into information searching and support group activity. Carers access Internet information to problem solve; however, they report doctors as their most preferred information source. They would like to have e-mail communication with Health Care Professionals to ask questions and clarify information. Participation in online support groups provides information tailored to individual needs and peer support.The Internet may be a primary or secondary source of information and can be used to access services. Routine assessment of carers Internet use, prescribing of Internet sites and e-mail communication with carers are possible areas for practice improvement. The current level of evidence is not ideal to influence policy development.Research is required to evaluate carer Internet use in the rapidly changing world of health and technology. Interactive Internet applications developed specifically for carer use have the potential to prepare, inform and support the carer in their ever-expanding health care role. The impact of these services on carer quality of life also requires investigation.

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