PubMed | Monash University, The Peter MacCallum Cancer Center, Cancer Action Victoria, Melbourne Health and 2 more.
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2016
This study aims to examine the unmet needs and psychological distress (anxiety and depression) in family caregivers of renal cell carcinoma survivors.A cross-sectional study design was used. Unmet needs were assessed with the Supportive Care Needs Survey-Partners and Caregivers (SCNS-P&C) questionnaire, and psychological distress was measured with the Hospital Anxiety and Depression Scale (HADS) in a telephone survey of 196 caregivers of renal cell carcinoma (RCC) survivors. Chi-square tests examined bivariate relationships, and multivariate logistic regression examined the associations between anxiety and depression and of unmet needs with caregivers experience of patients care, time spent caregiving, caregivers demographic characteristics and patients disease stage.Sixty-four percent of caregivers had at least one low, moderate or high unmet need, with 53% reporting at least three needs and 29% reporting 10 or more unmet needs (median 2, range 0-38). Elevated anxiety (HADS-A>8) and depression (HADS-D>8) were found in 29 and 11% of the sample, respectively. Psychological and emotional needs were associated with advanced cancer stage (stages 3 and 4) (OR 3.07, 95% CI 1.35-6.76) and with experience of care during surgery (OR 0.87, 95% CI 0.78-0.99). Healthcare service needs were associated with time spent caregiving, with caregivers spending >1h/day in the past week having three times higher odds (OR 3.44, 95% CI 1.52-7.72) than those not spending any time. Odds of experiencing information needs were lower in caregivers who were in a relationship (OR 0.20, 95% CI 0.04-0.83). Elevated anxiety (OR 1.59, 95% CI 1.09-2.33) and depression (OR 2.02, 95% CI 1.08-3.79) were associated with unmet information needs. Depression was also associated with experiences of care during treatment (OR 0.69, 95% CI 0.49-0.96).RCC caregivers unmet information needs are associated with elevated anxiety and depression. Improved experiences of cancer care are associated with lower odds of unmet needs and elevated depression in RCC caregivers.
PubMed | Monash Health, Monash University, Geelong Urology, The Peter MacCallum Cancer Center and Alfred Health
Type: Journal Article | Journal: The Medical journal of Australia | Year: 2016
To analyse the performance of the quality of prostate cancer (CaP) care over a 5-year period with reference to three quality indicators (QIs) reported by the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic):QI-1: Alignment with the modified Prostate Cancer Research International Active Surveillance (PRIAS) protocol guideline;QI-2: Timeliness of CaP care for men with high risk and locally advanced disease;QI-3: Positive surgical margins (PSMs) for organ-confined pathological T2 disease.Between 1 January 2009 and 31 December 2013, 4708 men diagnosed with CaP who met the QI-1, QI-2 or QI-3 inclusion criteria were recruited from Victorian hospitals.Outcome measures and statistical analysis: Trend analysis was conducted to monitor performance according to QI-1, QI-2 and QI-3. We used the autoregressive integrated moving average (ARIMA) model to account for any inherent autocorrelation in the data when analysing the monthly incidence of each indicator. Differences in the annual figures for the indicators across years were also analysed by aggregating data by year and applying the ARIMA model.There was a downward trend over the 5 years in the percentage of men with low risk disease who underwent active treatment (45% to 34%; P = 0.024), an upward trend in the percentage of those with high risk and locally advanced disease who received active treatment within 12 months of diagnosis (88% to 93%; P = 0.181), and a decline in PSM rate in men with pathological T2 disease after radical prostatectomy (21% to 12%; P = 0.036). Limitations of the study include the fact that the improvement in the QIs was detected using PCOR-Vic as a single population, but there may be institutional variations in quality improvement.Over 2009-2013, the performance of the Victorian health system improved according to the three processes of care indicators reported by the PCOR-Vic.
PubMed | Dana-Farber Cancer Institute, Monash University, Triphase Accelerator and The Peter MacCallum Cancer Center
Type: Journal Article | Journal: British journal of haematology | Year: 2016
Proteasome inhibitors (PIs) are highly active in multiple myeloma (MM) but resistance is commonly observed. All clinical stage PIs effectively inhibit chymotrypsin-like (CT-L) activity; one possible mechanism of resistance is compensatory hyperactivation of caspase-like (C-L) and trypsin-like (T-L) subunits, in response to CT-L blockade. Marizomib (MRZ), an irreversible PI that potently inhibits all three 20S proteasome subunits with a specificity distinct from other PIs, is currently in development for treatment of MM and malignant glioma. The pan-proteasome pharmacodynamic activity in packed whole blood and peripheral blood mononuclear cells was measured in two studies in patients with advanced solid tumours and haematological malignancies. Functional inhibition of all proteasome subunits was achieved with once- or twice-weekly MRZ dosing; 100% inhibition of CT-L was frequently achieved within one cycle at therapeutic doses. Concomitantly, C-L and T-L activities were either unaffected or increased, suggesting compensatory hyperactivation of these subunits. Importantly, this response was overcome by continued administration of MRZ, with robust inhibition of T-L and C-L (up to 80% and 50%, respectively) by the end of Cycle 2 and maintained thereafter. This enhanced proteasome inhibition was independent of tumour type and may underlie the clinical activity of MRZ in patients resistant to other PIs.
PubMed | University of Melbourne, The Peter MacCallum Cancer Center and IMP Research Institute of Molecular Pathology
Type: Review | Journal: The FEBS journal | Year: 2016
It is now well recognized that mutations, deregulated expression, and aberrant recruitment of epigenetic readers, writers, and erasers are fundamentally important processes in the onset and maintenance of many human tumors. The molecular, biological, and biochemical characteristics of a particular class of epigenetic erasers, the histone deacetylases (HDACs), have been extensively studied and small-molecule HDAC inhibitors (HDACis) have now been clinically approved for the treatment of human hemopoietic malignancies. This review explores our current understanding of the biological and molecular effects on tumor cells following HDACi treatment. The predominant responses include induction of tumor cell death and inhibition of proliferation that in experimental models have been linked to therapeutic efficacy. However, tumor cell-intrinsic responses to HDACi, including modulating tumor immunogenicity have also been described and may have substantial roles in mediating the antitumor effects of HDACi. We posit that the field has failed to fully reconcile the biological consequences of exposure to HDACis with the molecular events that underpin these responses, however progress is being made. Understanding the pleiotrophic activities of HDACis on tumor cells will hopefully fast track the development of more potent and selective HDACi that may be used alone or in combination to improve patient outcomes.
Murphy D.G.,The Peter MacCallum Cancer Center |
Murphy D.G.,Australian Prostate Cancer Research Center |
Bjartell A.,Lund University |
Ficarra V.,University of Padua |
And 9 more authors.
European Urology | Year: 2010
Context: Robot-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in widespread use for the management of localised prostate cancer (PCa). Many reports of the safety and efficacy of this procedure have been published. However, there are few specific reports of the limitations and complications of RALP. Objective: The primary purpose of this review is to ascertain the downsides of RALP by focusing on complications and limitations of this approach. Evidence acquisition: A Medline search of the English-language literature was performed to identify all papers published since 2001 relating to RALP. Papers providing data on technical failures, complications, learning curve, or other downsides of RALP were considered. Of 412 papers identified, 68 were selected for review based on their relevance to the objective of this paper. Evidence synthesis: RALP has the following principal downsides: (1) device failure occurs in 0.2-0.4% of cases; (2) assessment of functional outcome is unsatisfactory because of nonstandardised assessment techniques; (3) overall complication rates of RALP are low, although higher rates are noted when complications are reported using a standardised system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a steep learning curve exists, and although acceptable operative times can be achieved in <20 cases, positive surgical margin (PSM) rates may require experience with >80 cases before a plateau is achieved; (6) robotic assistance does not reduce the difficulty associated with obese patients and those with large prostates, middle lobes, or previous surgery, in whom outcomes are less satisfactory than in patients without such factors; (7) economic barriers prevent uniform dissemination of robotic technology. Conclusions: Many of the downsides of RALP identified in this paper can be addressed with longer-term data and more widespread adoption of standardised reporting measures. The significant learning curve should not be understated, and the expense of this technology continues to restrict access for many patients. © 2009 European Association of Urology.
PubMed | Walter and Eliza Hall Institute of Medical Research, The Peter MacCallum Cancer Center and University of Melbourne
Type: Journal Article | Journal: Immunology and cell biology | Year: 2016
Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8(+) T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8(+) T-cell response, the latter resulting in enhanced control of MC38-OVA tumors. These results reveal a novel role for Lgl-1 in the regulation of virus-specific T-cell responses and antitumor immunity.
Pinol J.,University of Barcelona |
Mir G.,CRAG CSIC IRTA UAB UB |
Mir G.,The Peter MacCallum Cancer Center |
Gomez-Polo P.,IRTA - Institute of Agricultural-Alimentary Research and Technology |
Agusti N.,IRTA - Institute of Agricultural-Alimentary Research and Technology
Molecular Ecology Resources | Year: 2015
The quantification of the biological diversity in environmental samples using high-throughput DNA sequencing is hindered by the PCR bias caused by variable primer-template mismatches of the individual species. In some dietary studies, there is the added problem that samples are enriched with predator DNA, so often a predator-specific blocking oligonucleotide is used to alleviate the problem. However, specific blocking oligonucleotides could coblock nontarget species to some degree. Here, we accurately estimate the extent of the PCR biases induced by universal and blocking primers on a mock community prepared with DNA of twelve species of terrestrial arthropods. We also compare universal and blocking primer biases with those induced by variable annealing temperature and number of PCR cycles. The results show that reads of all species were recovered after PCR enrichment at our control conditions (no blocking oligonucleotide, 45 °C annealing temperature and 40 cycles) and high-throughput sequencing. They also show that the four factors considered biased the final proportions of the species to some degree. Among these factors, the number of primer-template mismatches of each species had a disproportionate effect (up to five orders of magnitude) on the amplification efficiency. In particular, the number of primer-template mismatches explained most of the variation (~3/4) in the amplification efficiency of the species. The effect of blocking oligonucleotide concentration on nontarget species relative abundance was also significant, but less important (below one order of magnitude). Considering the results reported here, the quantitative potential of the technique is limited, and only qualitative results (the species list) are reliable, at least when targeting the barcoding COI region. © 2014 John Wiley & Sons Ltd.
Ramsbottom K.M.,The Peter MacCallum Cancer Center
Immunology and Cell Biology | Year: 2015
Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8+ T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8+ T-cell response, the latter resulting in enhanced control of MC38-OVA tumors. These results reveal a novel role for Lgl-1 in the regulation of virus-specific T-cell responses and antitumor immunity.Immunology and Cell Biology advance online publication, 22 September 2015; doi:10.1038/icb.2015.82. © 2015 Australasian Society for Immunology Inc.
West A.C.,The Peter MacCallum Cancer Center |
Smyth M.J.,QIMR Berghofer Medical Research Institute |
Smyth M.J.,University of Queensland |
Johnstone R.W.,The Peter MacCallum Cancer Center |
Johnstone R.W.,University of Melbourne
OncoImmunology | Year: 2014
Histone deacetylase inhibitors (HDACis) are known to exert immunomodulatory effects. We have recently demonstrated that the therapeutic efficacy of HDACis against aggressive B-cell lymphoma and colon carcinoma relies on a functional immune system, in particular on the production of interferon γ (IFNγ). Our findings provide a rationale for the combination of HDACis with immunotherapeutic agents in the clinic. © 2014 Landes Bioscience.