Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. We used molecular profiling combined with functional ...assays to investigate the role of these cells in human renal cell carcinoma (RCC). Blood monocytes from RCC patients displayed a tumor-promoting transcriptional profile that supported functions like angiogenesis and invasion. Induction of this protumor phenotype required an interleukin-1 receptor (IL-1R)-dependent mechanism. Indeed, targeting of IL-1-IL-1R axis in a human RCC xenograft model abrogated the protumor phenotype of tumor-associated macrophages (TAMs) and reduced tumor growth in vivo. Supporting this, meta-analysis of gene expression from human RCC tumors showed IL1B expression to correlate with myelomonocytic markers, protumor genes, and tumor staging. Analyzing RCC patient tumors confirmed the protumor phenotype of TAMs. These data provide direct evidence for a tumor-promoting role of monocytes and macrophages in human cancer and indicate IL-1-IL-1R as a possible therapeutic target.
•Monocytes and macrophages show a protumor phenotype in a human cancer setting•The protumor phenotype is regulated by an IL-1 receptor-dependent mechanism•Targeting this mechanism abrogated macrophage protumor phenotype and tumor in vivo
Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. Biswas and colleagues provide transcriptional, functional, and mechanistic data demonstrating a tumor-promoting phenotype of these cells in a human cancer setting.
Objective
The aim of this study was to review clinical outcomes and prognosis of paediatric patients with acute lymphoblastic leukaemia (ALL) with TCF3‐PBX1 rearrangement.
Patients
All children in ...Hong Kong diagnosed with ALL with TCF3‐PBX1 rearrangement over the past two decades were included.
Methods
Six hundred and twenty‐four newly diagnosed patients with ALL from four consecutive studies were enrolled from 1997 to 2016. Patients carrying TCF3‐PBX1 rearrangement and patients at intermediate risk without the gene expression were compared for clinical characteristics, overall survival and event‐free survival (EFS).
Results
The TCF3‐PBX1 rearrangement was detected in 30 of 624 patients (4.8%). Results were consistent across the consecutive clinical trials employed in the past two decades. Compared with 239 intermediate risk patients without TCF3‐PBX1 rearrangement, the 5‐year overall survival and EFS for patients with TCF3‐PBX1 rearrangement was superior, with both at 100% (P = 0.12 and P = 0.029).
Conclusion
This population‐based study over the past 20 years demonstrated that patients with TCF3‐PBX1 rearrangement had favourable EFS compared with other intermediate risk patients treated with a similar chemotherapy backbone.
Central serous chorioretinopathy (CSCR) is a leading cause of central vision impairment in the working-age population with male predilection. Knowledge about the genetic basis of CSCR and its male ...predilection remained limited. This study aimed to evaluate the association patterns of multiple gene variants in chronic CSCR (cCSCR) in Chinese patients.
This case-control genetic association study included 531 patients with cCSCR and 2383 controls from two independent Chinese cohorts. Nine single-nucleotide polymorphisms (SNPs) of six genes, namely CFH, NR3C2, GATA5, VIPR2, TNFRSF10A, and ARMS2, were genotyped in all subjects. The main outcome measures were the association of individual single-nucleotide polymorphism (SNP) with cCSCR, the sex-stratification effects of individual SNP, and joint effects of different SNPs on cCSCR.
Association results in the two cohorts were consistent with low heterogeneities. In the combined analysis, SNPs CFH rs800292 (odds ratio OR = 1.25, P = 0.0020), CFH rs1329428 (OR = 1.23, P = 0.0037), and TNFRSF10A rs13278062 (OR = 1.43, P = 0.0014) were significantly associated with cCSCR. In stratification analysis by sex, 3 SNPs in CFH, rs3753394, rs800292, and rs1329428, were associated with cCSCR in male patients, but not in female patients. Joint analysis revealed that subjects homozygous for the risk alleles of CFH rs800292 and TNFRSF10A rs13278062 had over 4-fold of increased risk of cCSCR when compared with subjects homozygous for the non-risk alleles (OR = 4.06, P = 2.30 × 10-5).
This study revealed main and joint effects of SNPs in CFH and TNFRSF10A on cCSCR, and suggested CFH as a potential genetic factor underlying the male predilection of cCSCR. Further replication in other study populations is needed.
Haemoglobin Bart's hydrops fetalis syndrome was once considered a fatal condition. However, advances over the past two decades have enabled survival of affected patients. Data relating to their ...morbidities and outcomes will help medical specialists formulate a management plan and parental counselling.
All babies with the syndrome who survived beyond the neonatal period and were subsequently managed long-term in eight public hospitals in Hong Kong from 1 January 1996 to 31 December 2015 were included. Patient and parent characteristics, antenatal care, reasons for continuation of pregnancy, intrauterine interventions, perinatal course, presence of congenital malformations, stem-cell transplantation details, and long-term neurodevelopmental outcomes were reviewed.
A total of nine patients were identified, of whom five were female and four male. The median follow-up duration was 7 years. All were Chinese and were homozygous for the Southeast Asian α-thalassaemia deletion. Five of the nine mothers received antenatal care at a public hospital and opted to continue the pregnancy after antenatal diagnosis and counselling. Despite intrauterine transfusions, all babies were born with respiratory depression and required intubation and mechanical ventilation during the neonatal period. Hypospadias was identified in all four male infants. Growth retardation, global developmental delay, and residual neurological deficits were noted in two-thirds of the patients. Haematopoietic stem-cell transplantation was performed in two patients, who became transfusion-independent.
Survival of patients with Bart's hydrops fetalis syndrome is possible but not without short- and long-term complications; local epidemiology is comparable to that documented for an international registry. Detailed antenatal counselling of parents with a non-judgemental attitude and cautious optimism are imperative.
To provide a synopsis of current thalassaemia major patient care in Hong Kong.
Retrospective study.
All haematology units of the Hospital Authority in Hong Kong.
All patients with thalassaemia major ...with regular transfusion.
To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy.
The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.
LINC-20. INFANT BRAIN TUMOURS IN HONG KONG Shing, Matthew M K; Ku, Dennis T L; Chan, Godfrey C F ...
Neuro-oncology (Charlottesville, Va.),
12/2020, Letnik:
22, Številka:
Supplement_3
Journal Article
Recenzirano
Odprti dostop
Abstract
OBJECTIVES
To review the clinical features, pathology and survivals of infants with brain tumours.
METHODS
A retrospective review of the clinical findings, pathology, treatment and survival ...outcome in infants with brain tumours.
RESULTS
From 1999 to 2018, there were 507 children (<18 years) who were diagnosed to have brain tumours in Hong Kong. The patients were treated in five public hospitals. The clinical data were collected by the Hong Kong Paediatric Haematology and Oncology Study Group, and were cross-checked with the data of the Hong Kong Cancer Registry. In this group of patients, there were 36 infants (birth to 365 days of age) i.e. 7.1% of the whole group. Both benign and malignant brain tumours were included, while non-neoplastic lesions were excluded. On average, there was 1.89 cases per year. The pathology of the tumours were astrocytoma (n= 8), medulloblastoma (n=6), germ cell tumour (n=6), PNET (n=5), ATRT (n=4), choroid plexus tumours (n=3), ependymoma (n=2), craniopharyngioma (n= 1) and ganglioglioma (n= 1). These infants were treated according to their clinical conditions and prognosis, with operation, chemotherapy or both. Radiotherapy was withheld or postponed to older age. Some patients only received palliative care due to the poor neurological status or prognosis. The overall survivals of children younger than 18 years old vs infants were 67.3% (±2.3) vs 50.5%(±9.2) respectively, while the event free survivals were 64.4% (±2.4) and 43.5% (±8.8) at 10-years respectively.
CONCLUSION
Infants with brain tumours have different pathology and inferior outcome.
To provide a synopsis of current haemophilia care in Hong Kong.
Retrospective survey.
All haematology units of the Hospital Authority in Hong Kong.
All patients with haemophilia A and haemophilia B.
...To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further.
A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.
Abstract only
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Background: The presence of AR-V7 in metastatic castrate resistant prostate cancer (mCRPC) men has been associated with worse outcome in men initiated on 2nd generation androgen ...receptor signalling inhibitors (ARSI) in the Caucasian population. A multinational study was conducted to investigate this in the Asian population. Methods: mCRPC patients were recruited prospectively across 5 countries. Blood samples were collected and processed from patients with progressive disease immediately before the initiation of a new treatment and at progression. AR-V7 detection were performed using 3 methods: CTC enrichment followed by automated immunofluorescent staining (Clearbridge CB), CTC enrichment followed by reverse-transcription PCR analysis (IBN), and the AdnaTest Prostate Cancer(Adna) platform for CTC analysis and detection. Only blood samples collected in Singapore underwent all 3 methods of detecting AR-V7. Comparison of AR-V7 prevalence using the 3 detection methods were done on patients with the AdnaTest platform as gold standard. We examined associations between AR-V7 status and PSA response rates, PSA progression free survival and overall survival(OS). Results: 102 patients were recruited. 72 patients had ARSi while 30 patients had chemotherapy. 66 patients were included for the comparison of AR-V7 detection methods. AR-V7 prevalence rate was 14.3% (95% CI 4.8-30.3), 21.6% (95% CI 12.9-32.7) and 33.7% (95% CI 24.6-43.8) based on Adna, CB and IBN respectively. Concordance between Adna and CB was 75% while Adna and IBN was 68%. AR-V7- patients had a trend towards higher PSA response, lower risk of PSA progression as compared to AR-V7+ patients. AR-V7- patients had a significantly lower risk of death as compared to AR-V7+ patients detected by Adna and IBN platforms but not the CB platform. The association between ARV7 status and outcomes did not vary when compared across treatment groups. Conclusions: AR-V7 positivity in Asian mCRPC patients is consistent with the data reported in Western populations with lower PSA response rates, PSA progression free survival and OS. This data suggest that ARV7 is more likely a prognostic than a predictive biomarker. Clinical trial information: 2015/2797.
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