Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide

Temozolomide (TMZ) is standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and may be associated with the development of TMZ resistance. Oxygen therapy has previously been reported to potentiate the effect of chemotherapy in cancer. In this study, we investigated whether hyperoxia can enhance the TMZ-induced cytotoxicity of human GBM cells, and whether and how it would resensitize TMZ-resistant GBM cells to TMZ. TMZ-sensitive human GBM cells (D54-S and U87-S) were treated with TMZ to develop isogenic subclones of TMZ-resistant cells (D54-R and U87-R). All cell lines were then exposed to different oxygen levels (1, 21, 40, or 80 %), with or without concomitant TMZ treatment, before assessment of cell cytotoxicity and morphology. Cell death and survival pathways elicited by TMZ and/or hyperoxia were elucidated by western blotting. Our results showed that TMZ sensitivity of both chemo-sensitive and resistant cells was enhanced significantly under hyperoxia. At the cell line-specific optimum oxygen concentration (D54-R, 80 %; U87-R, 40 %), resistant cells had the same response to TMZ as the parent chemosensitive cells under normoxia via the caspase-dependent pathway. Both TMZ and hyperoxia were associated with increased phosphorylation of ERK p44/42 MAPK (Erk1/2), but to a lesser extent in D54-R cells, suggesting that Erk1/2 activity may be involved in regulation of hyperoxia and TMZ-mediated cell death. Overall, hyperoxia enhanced TMZ toxicity in GBM cells by induction of apoptosis, possibly via MAPK-related pathways. Induced hyperoxia is a potentially promising approach for treatment of TMZ-resistant GBM.published_or_final_versio

The Osteoporosis Society of Hong Kong (OSHK): 2013 OSHK Guideline for Clinical Management of Postmenopausal Osteoporosis in Hong Kong

published_or_final_versio

Potential roles of cytoskeletal protein in glioblastoma chemoresistance

Conference Theme: Brain Attack: A New EraPosters: no. P-14INTRODUCTION: Glioblastoma is a highly malignant neoplasm for which temozolomide is currently the standard chemotherapeutic agent. Adducin 3 (ADD3) is a cytoskeletal protein associated with chemoresistance but its role in glioblastoma has not been investigated ...postprin

Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study

Background The CovidSurg-Cancer Consortium aimed to explore the impact of COVID-19 in surgical patients and services for solid cancers at the start of the pandemic. The CovidSurg-Gynecologic Oncology Cancer subgroup was particularly concerned about the magnitude of adverse outcomes caused by the disrupted surgical gynecologic cancer care during the COVID-19 pandemic, which are currently unclear. Objective This study aimed to evaluate the changes in care and short-term outcomes of surgical patients with gynecologic cancers during the COVID-19 pandemic. We hypothesized that the COVID-19 pandemic had led to a delay in surgical cancer care, especially in patients who required more extensive surgery, and such delay had an impact on cancer outcomes. Study Design This was a multicenter, international, prospective cohort study. Consecutive patients with gynecologic cancers who were initially planned for nonpalliative surgery, were recruited from the date of first COVID-19-related admission in each participating center for 3 months. The follow-up period was 3 months from the time of the multidisciplinary tumor board decision to operate. The primary outcome of this analysis is the incidence of pandemic-related changes in care. The secondary outcomes included 30-day perioperative mortality and morbidity and a composite outcome of unresectable disease or disease progression, emergency surgery, and death. Results We included 3973 patients (3784 operated and 189 nonoperated) from 227 centers in 52 countries and 7 world regions who were initially planned to have cancer surgery. In 20.7% (823/3973) of the patients, the standard of care was adjusted. A significant delay (>8 weeks) was observed in 11.2% (424/3784) of patients, particularly in those with ovarian cancer (213/1355; 15.7%; P<.0001). This delay was associated with a composite of adverse outcomes, including disease progression and death (95/424; 22.4% vs 601/3360; 17.9%; P=.024) compared with those who had operations within 8 weeks of tumor board decisions. One in 13 (189/2430; 7.9%) did not receive their planned operations, in whom 1 in 20 (5/189; 2.7%) died and 1 in 5 (34/189; 18%) experienced disease progression or death within 3 months of multidisciplinary team board decision for surgery. Only 22 of the 3778 surgical patients (0.6%) acquired perioperative SARS-CoV-2 infections; they had a longer postoperative stay (median 8.5 vs 4 days; P<.0001), higher predefined surgical morbidity (14/22; 63.6% vs 717/3762; 19.1%; P<.0001) and mortality (4/22; 18.2% vs 26/3762; 0.7%; P<.0001) rates than the uninfected cohort. Conclusion One in 5 surgical patients with gynecologic cancer worldwide experienced management modifications during the COVID-19 pandemic. Significant adverse outcomes were observed in those with delayed or cancelled operations, and coordinated mitigating strategies are urgently needed

Cognitive impairment of Chinese patients with multiple sclerosis and neuromyelitis optica

Session: Clinical aspects of MS - MS symptoms: abstract no. P878INTRODUCTION: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are important central nervous system inflammatory demyelinating disorders. Cognitive impairment is increasingly recognized in both MS and NMOSD. METHODS: We studied cognitive functions of Chinese MS and NMOSD patients followed up in QMH by using a Chinese version of Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRBN). The BRBN consists of five groups of tests: 1) Symbol Digit Modalities Test (SDMT) and 2) Paced Auditory Serial Addition Test (PASAT) for sustained attention, concentration and speed of information processing, 3) Selective Reminding Test (SRT) for verbal immediate and delayed recall memory, 4) 10/36 Spatial Recall Test (SPART) for spatial immediate and delayed recall memory, and 5) Word List Generation Test (WLG) for verbal fluency on semantic stimulus; yielding total 9 test scores. An abnormal score is defined as below the fifth percentile of the normative value derived from healthy subjects. Patients with abnormal scores in 3 or more tests were diagnosed as having cognitive impairment. RESULTS: 30 healthy subjects (16 men, mean age 37.3 years, range 21-56), 17 NMOSD patients (15 women, mean age 47 years, range 28-69) and 21 MS patients (14 women, mean age 40.5 years, range 18-59) were studied. The mean disease duration was 80.5 months, the mean latest EDSS score was 2.7, 13 (76.%%) were AQP4 antibody +ve and 10 (58.8%) had MRI brain abnormalities for the NMOSD patients. The mean disease duration was 141.7 months and the mean latest EDSS score was 3.5 for the MS patients. Among the 17 NMOSD patients, 5 (31.3%) had impaired SDMT, 6 (35.3%) had impaired SRT, 7 (41.2%) had impaired SPART, 7 (41.2%) had impaired PASAT and 7 (41.2%) had impaired WLG. Overall, 8 NMOSD patients (47.1%) had cognitive impairment. Among the 21 MS patients, 15 (71.4%) had impaired SDMT, 10 (47.6%) had impaired SRT, 9 (42.9%) had impaired SPART, 14 (66.7%) had impaired PASAT and 14 (66.7%) had impaired WLG). Overall, 15 MS patients (71.4%) had cognitive impairment. CONCLUSION: Cognitive impairment is common among NMOSD and MS patients

Changes of MGMT and CD133 methylation status in glioma cells in response to chronic temozolomide treatment

The 19th Annual Scientific Meeting of the Hong Kong Neurosurgical Society, Hong Kong, December 2010

The potential use of microRNA-21 inhibitors to overcome temozolomide resistance in glioblastoma multiforme

The 7th Meeting of the Asian Society for Neuro-oncology (ASNO 2010), Seoul, Korea, 10-12 June 2010

Proteomic alterations associated with acquired temozolomide resistance in human malignant gliomas: the role of proly 4-hydroxylase, beta polypeptide

The 19th Annual Scientific Meeting of the Hong Kong Neurosurgical Society, Hong Kong, December 2010

Overcoming temozolomide resistance in glioblastoma multiforme: the potential application of microRNA inhibition

The 19th Annual Scientific Meeting of the Hong Kong Neurosurgical Society, Hong Kong, December 2010