Displaying publications 1 - 20 of 58 in total

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  1. Azzani M, Azhar ZI, Ruzlin ANM, Wee CX, Samsudin EZ, Al-Harazi SM, et al.
    BMC Cancer, 2024 Jan 05;24(1):40.
    PMID: 38182993 DOI: 10.1186/s12885-023-11814-1
    BACKGROUND: Colorectal cancer (CRC) is the third most common cancer type worldwide. Colorectal cancer treatment costs vary between countries as it depends on policy factors such as treatment algorithms, availability of treatments and whether the treatment is government-funded. Hence, the objective of this systematic review is to determine the prevalence and measurements of financial toxicity (FT), including the cost of treatment, among colorectal cancer patients.

    METHODS: Medline via PubMed platform, Science Direct, Scopus, and CINAHL databases were searched to find studies that examined CRC FT. There was no limit on the design or setting of the study.

    RESULTS: Out of 819 papers identified through an online search, only 15 papers were included in this review. The majority (n = 12, 80%) were from high-income countries, and none from low-income countries. Few studies (n = 2) reported objective FT denoted by the prevalence of catastrophic health expenditure (CHE), 60% (9 out of 15) reported prevalence of subjective FT, which ranges from 7 to 80%, 40% (6 out of 15) included studies reported cost of CRC management- annual direct medical cost ranges from USD 2045 to 10,772 and indirect medical cost ranges from USD 551 to 795.

    CONCLUSIONS: There is a lack of consensus in defining and quantifying financial toxicity hindered the comparability of the results to yield the mean cost of managing CRC. Over and beyond that, information from some low-income countries is missing, limiting global representativeness.

  2. Rengganaten V, Huang CJ, Wang ML, Chien Y, Tsai PH, Lan YT, et al.
    BMC Cancer, 2023 Nov 10;23(1):1088.
    PMID: 37950151 DOI: 10.1186/s12885-023-11571-1
    BACKGROUND: Cancer stem cells form a rare cell population in tumors that contributes to metastasis, recurrence and chemoresistance in cancer patients. Circular RNAs (circRNAs) are post-transcriptional regulators of gene expression that sponge targeted microRNA (miRNAs) to affect a multitude of downstream cellular processes. We previously showed in an expression profiling study that circZNF800 (hsa_circ_0082096) was up-regulated in cancer stem cell-enriched spheroids derived from colorectal cancer (CRC) cell lines.

    METHODS: Spheroids were generated in suspension spheroidal culture. The ZNF800 mRNA, pluripotency stem cell markers and circZNF800 levels were determined by quantitative RT-PCR. CircZNF800-miRNA interactions were shown in RNA pulldown assays and the miRNA levels determined by stem-loop qRT-PCR. The effects of circZNF800 on cell proliferation were tested by EdU staining followed by flowcytometry. Expression of stem cell markers CD44/CD133, Lgr5 and SOX9 was demonstrated in immunofluorescence microscopy. To manipulate the cellular levels of circZNF800, circZNF800 over-expression was achieved via transfection of in vitro synthesized and circularized circZNF800, and knockdown attained using a CRISPR-Cas13d-circZNF800 vector system. Xenografted nude mice were used to demonstrate effects of circZNF800 over-expression and knockdown on tumor growth in vivo.

    RESULTS: CircZNF800 was shown to be over-expressed in late-stage tumor tissues of CRC patients. Data showed that circZNF800 impeded expression of miR-140-3p, miR-382-5p and miR-579-3p while promoted the mRNA levels of ALK/ACVR1C, FZD3 and WNT5A targeted by the miRNAs, as supported by alignments of seed sequences between the circZNF800-miRNA, and miRNA-mRNA paired interactions. Analysis in CRC cells and biopsied tissues showed that circZNF800 positively regulated the expression of intestinal stem cell, pluripotency and cancer stem cell markers, and promoted CRC cell proliferation, spheroid and colony formation in vitro, all of which are cancer stem cell properties. In xenografted mice, circZNF800 over-expression promoted tumor growth, while circZNF800 knockdown via administration of CRISPR Cas13d-circZNF800 viral particles at the CRC tumor sites impeded tumor growth.

    CONCLUSIONS: CircZNF800 is an oncogenic factor that regulate cancer stem cell properties to lead colorectal tumorigenesis, and may be used as a predictive marker for tumor progression and the CRISPR Cas13d-circZNF800 knockdown strategy for therapeutic intervention of colorectal cancer.

  3. Qyi YZ, Aung HH, Aye SN, Tung WS, Naing C
    BMC Cancer, 2023 Oct 24;23(1):1027.
    PMID: 37875868 DOI: 10.1186/s12885-023-11509-7
    BACKGROUND: Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies.

    METHODS: This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.

    RESULTS: Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90-1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38-4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74-2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07-1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12-11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76-2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13-2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89-1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05-1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34-4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.

    CONCLUSIONS: The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.

  4. Andrew Tong JW, Hee MQ
    BMC Cancer, 2023 Oct 06;23(1):947.
    PMID: 37803291 DOI: 10.1186/s12885-023-11427-8
    BACKGROUND: Breast cancer is one of the world's most prevalent cancer and the most common type of cancer in Malaysia. Interestingly, breast cancer in young women is more aggressive compared to older women and the survival rate among these groups of individuals is poor. Thus, breast cancer awareness is essential among young women as early detection is possible and treatment will be effective during which the disease is curable. Hence, the purpose of this study is to design and evaluate the impact of an educational game on breast cancer awareness among female university students in Malaysia.

    METHODS: This is a one-group pre-and post-intervention pilot study. It was conducted in Private and public higher education institutions around Malaysia. An online education game was created and used as the intervention. A self-administered questionnaire was administered to the participants during the pre-and post-intervention test to evaluate the online educational game on breast cancer awareness.

    RESULTS: A total of 52 responses were collected. The mean age of the participants was 21.98 (SD = 1.896) years. The findings showed a statistically significant median increase (p 

  5. Mei TTY, Aung HH, Tung WS, Naing C
    BMC Cancer, 2023 Sep 08;23(1):842.
    PMID: 37684564 DOI: 10.1186/s12885-023-11323-1
    BACKGROUND: The carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies.

    METHODS: This study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size.

    RESULTS: Fifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45-0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43-0.85) and allelic models (OR: 0.79, 95% CI: 0.64-0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02-2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03-3.86, and homozygous models (OR: 2.18, 95% CI: 1.13-4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the - 1082 A/G or -819 T/C.

    CONCLUSIONS: Findings suggest that IL-10 (-1082 A/G and - 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and - 819 T/C) with different ethnicities are recommended.

  6. Liam CK, Yew CY, Pang YK, Wong CK, Poh ME, Tan JL, et al.
    BMC Cancer, 2023 Jul 14;23(1):659.
    PMID: 37452277 DOI: 10.1186/s12885-023-11156-y
    BACKGROUND: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking.

    METHODS: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked 

  7. Kuan JW, Su AT, Wahab M, Hamdan A, Hashim J, Kiyu A, et al.
    BMC Cancer, 2023 Jun 19;23(1):563.
    PMID: 37337159 DOI: 10.1186/s12885-023-10988-y
    BACKGROUND: Published epidemiological studies of haematological cancers are few. Hereby we present a 20-year epidemiological data of haematological cancers in Sarawak from a population-based cancer registry.

    METHODS: Haematological cancer cases with ICD-10 coded C81-C96 and ICD-O coded /3 diagnosed from 1996 to 2015 were retrieved from Sarawak Cancer Registry. Adult was defined as those 15 years and above. Incidence rate (IR) was calculated based on yearly Sarawak citizen population stratified to age, gender, and ethnic groups. Age-standardised IR (ASR) was calculated using Segi World Standard Population.

    RESULTS: A total of 3,947 cases were retrieved and analysed. ASR was 10 and male predominance (IR ratio 1.32, 95%CI 1.24,1.41). Haematological cancers generally had a U-shaped distribution with lowest IR at age 10-14 years and exponential increment from age 40 years onwards, except acute lymphoblastic leukaemia (ALL) with highest IR in paediatric 2.8 versus adult 0.5. There was a significant difference in ethnic and specific categories of haematological cancers, of which, in general, Bidayuh (IR ratio 1.13, 95%CI 1.00, 1.27) and Melanau (IR ratio 0.54, 95%CI 0.45, 0.65) had the highest and lowest ethnic-specific IR, respectively, in comparison to Malay. The ASR (non-Hodgkin lymphoma, acute myeloid leukaemia, ALL, chronic myeloid leukaemia, and plasma cell neoplasm) showed a decreasing trend over the 20 years, -2.09 in general, while Hodgkin lymphoma showed an increasing trend of + 2.80. There was crude rate difference between the 11 administrative divisions of Sarawak.

    CONCLUSIONS: This study provided the IR and ASR of haematological cancers in Sarawak for comparison to other regions of the world. Ethnic diversity in Sarawak resulted in significant differences in IR and ASR.

  8. Jeon AJ, Teo YY, Sekar K, Chong SL, Wu L, Chew SC, et al.
    BMC Cancer, 2023 Feb 03;23(1):118.
    PMID: 36737737 DOI: 10.1186/s12885-022-10444-3
    BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).

    METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.

    RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.

    DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

  9. Pivot X, Manikhas AG, Shamrai V, Dzagnidze G, Soo Hoo HF, Kaewkangsadan V, et al.
    BMC Cancer, 2023 Jan 31;23(1):112.
    PMID: 36721174 DOI: 10.1186/s12885-023-10574-2
    BACKGROUND: The TROIKA trial established that HD201 and trastuzumab were equivalent in terms of primary endpoints (total pathological complete response) following neoadjuvant treatment. The objective of the present analysis was to compare survival outcomes and final safety.

    METHODS: In the TROIKA trial, patients with ERBB2-positive early breast cancer were randomized and treated with either HD201 or the referent trastuzumab. Eligible patients received 8 cycles of either HD201 or referent trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in combination with 8 cycles of chemotherapy (4 cycles of docetaxel, 75 mg/m2, followed by 4 cycles of epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) in the neoadjuvant setting. The patients then underwent surgery followed by 10 cycles of adjuvant HD201 or referent trastuzumab according to their initial randomization to complete one year of trastuzumab-directed therapy. Event-free and overall survival rates were calculated using Kaplan-Meier analysis. The hazard ratio for event-free survival was estimated by Cox proportional hazards regression.

    RESULTS: The final analysis was performed after all patients completed the study at a median follow-up of 37.7 months (Q1-Q3, 37.3-38.1 months). A total of 502 randomized patients received either HD201 or the referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. In this population, the 3-year event-free survival rates were 85.6% (95% CI: 80.28-89.52) and 84.9% (95% CI: 79.54-88.88) in the HD201 and referent trastuzumab groups, respectively (log rank p = 0.938) (HR 1.02, 95% CI: 0.63-1.63; p = 0.945). The 3-year overall survival rates were comparable between the HD201 (95.6%; 95% CI: 91.90-97.59) and referent trastuzumab treatment groups (96.0%, 95% CI: 92.45-97.90) (log rank p = 0.606). During the posttreatment follow-up period, adverse events were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the reference trastuzumab groups, respectively. Serious adverse events were rare and none of which were related to the study treatment.

    CONCLUSIONS: This final analysis of the TROIKA trial further confirms the comparable efficacy and safety of HD201 and trastuzumab.

    TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03013504.

  10. Schliemann D, Ramanathan K, Ibrahim Tamin NSB, O'Neill C, Cardwell CR, Ismail R, et al.
    BMC Cancer, 2023 Jan 06;23(1):22.
    PMID: 36609260 DOI: 10.1186/s12885-022-10487-6
    INTRODUCTION: The Colorectal Cancer Screening Intervention for Malaysia (CRC-SIM) was a CRC study of home-based testing designed to improve low screening uptake using the immunochemical fecal occult blood test (iFOBT) in Malaysia.

    METHODS: This quasi-experimental study was informed by the Implementation Research Logic Model and evaluated with the RE-AIM framework. Trained data collectors recruited by phone, randomly selected, asymptomatic adults aged 50-75 years from Segamat District, who previously completed a health census form for the South East Asia Community Observatory (SEACO). Participants were posted an iFOBT kit and asked to return a photo of the completed test for screening by health care professionals. A regression analysis of evaluation data was conducted to identify which variables were associated with the outcome indicators of 'study participation' and 'iFOBT completion' and the CRC-SIM was evaluated in terms of its appropriateness, feasibility and acceptability.

    RESULTS: Seven hundred forty-seven eligible adults (52%) agreed to participate in this study and received an iFOBT kit. Participation was significantly lower amongst Chinese Malaysians (adjusted OR 0.45, 95% CI 0.35 - 0.59, p<0.001) compared to Malays and amongst participants from the rural sub-district (Gemereh) (adjusted OR 0.71, 95% CI 0.54 - 0.92, p=0.011) compared to the urban sub-district (Sungai Segamat). Less than half of participants (42%, n=311/747) completed the iFOBT. Test-kit completion was significantly higher amongst Chinese Malaysians (adjusted OR 3.15, 95% CI 2.11 - 4.69, p<0.001) and lower amongst participants with a monthly household income ≥RM 4,850 (adjusted OR 0.58, 95% CI 0.39 - 0.87, p=0.009) compared to participants with a lower household income. The main reported reason for non-participation was 'not interested' (58.6%) and main implementation challenges related to invalid photographs from participants and engaging iFOBT positive participants in further clinic consultations and procedures.

    CONCLUSION: Home-testing for CRC (test completion) appeared to be acceptable to only around one-fifth of the target population in Malaysia. However, mindful of the challenging circumstances surrounding the pandemic, the CRC-SIM merits consideration by public health planners as a method of increasing screening in Malaysia, and other low- and middle-income countries.

  11. Zeng R, Li H, Jia L, Lee SH, Jiang R, Zhang Y, et al.
    BMC Cancer, 2022 Dec 16;22(1):1317.
    PMID: 36527000 DOI: 10.1186/s12885-022-10369-x
    BACKGROUND: Acquired chemo-drug resistance constantly led to the failure of chemotherapy for malignant cancers, consequently causing cancer relapse. Hence, identifying the biomarker of drug resistance is vital to improve the treatment efficacy in cancer. The clinical prognostic value of CYP24A1 remains inconclusive, hence we aim to evaluate the association between CYP24A1 and the drug resistance in cancer patients through a meta-analysis approach.

    METHOD: Relevant studies detecting the expression or SNP of CYP24A1 in cancer patients up till May 2022 were systematically searched in four common scientific databases including PubMed, EMBASE, Cochrane library and ISI Web of Science. The pooled hazard ratios (HRs) indicating the ratio of hazard rate of survival time between CYP24A1high population vs CYP24A1low population were calculated. The pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were used to explore the association between CYP24A1's expression or SNP with survival, metastasis, recurrence, and drug resistance in cancer patients.

    RESULT: Fifteen studies were included in the meta-analysis after an initial screening according to the inclusion and exclusion criteria. There was a total of 3784 patients pooled from all the included studies. Results indicated that higher expression or SNP of CYP24A1 was significantly correlated with shorter survival time with pooled HRs (95% CI) of 1.21 (1.12, 1.31), metastasis with pooled ORs (95% CI) of 1.81 (1.11, 2.96), recurrence with pooled ORs (95% CI) of 2.14 (1.45, 3.18) and drug resistance with pooled HRs (95% CI) of 1.42 (1.17, 1.68). In the subgroup analysis, cancer type, treatment, ethnicity, and detection approach for CYP24A1 did not affect the significance of the association between CYP24A1 expression and poor prognosis.

    CONCLUSION: Findings from our meta-analysis demonstrated that CYP24A1's expression or SNP was correlated with cancer progression and drug resistance. Therefore, CYP24A1 could be a potential molecular marker for cancer resistance.

  12. Sharmni Vishnu K, Win TT, Aye SN, Basavaraj AK
    BMC Cancer, 2022 Nov 05;22(1):1139.
    PMID: 36335316 DOI: 10.1186/s12885-022-10225-y
    BACKGROUND: Triple negative breast cancer (TNBC) is clinically aggressive breast cancer with a poor prognosis. Approximately 20% of TNBC has been found to express programmed death ligand 1 (PD-L1), making it a potential therapeutic target. As a PD-L1 inhibitor, atezolizumab is a recently approved immunotherapeutic drug for TNBC, this meta-analysis (MA) was aimed to review the randomized controlled trial studies (RCTs) of combined atezolizumab and nab-paclitaxel in the treatment of TNBC and synthesize the evidence-based results on its effectiveness and safety.

    METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).

    RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).

    CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.

    TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).

  13. Schliemann D, Ramanathan K, Matovu N, O'Neill C, Kee F, Su TT, et al.
    BMC Cancer, 2021 Oct 19;21(1):1125.
    PMID: 34666704 DOI: 10.1186/s12885-021-08809-1
    BACKGROUND: Low- and middle-income countries (LMICs) experienced increasing rates of colorectal cancer (CRC) incidence in the last decade and lower 5-year survival rates compared to high-income countries (HICs) where the implementation of screening and treatment services have advanced. This review scoped and mapped the literature regarding the content, implementation and uptake of CRC screening interventions as well as opportunities and challenges for the implementation of CRC screening interventions in LMICs.

    METHODS: We systematically followed a five-step scoping review framework to identify and review relevant literature about CRC screening in LMICs, written in the English language before February 2020. We searched Medline, Embase, Web of Science and Google Scholar for studies targeting the general, asymptomatic, at-risk adult population. The TIDieR tool and an implementation checklist were used to extract data from empirical studies; and we extracted data-informed insights from policy reviews and commentaries.

    RESULTS: CRC screening interventions (n = 24 studies) were implemented in nine middle-income countries. Population-based screening programmes (n = 11) as well as small-scale screening interventions (n = 13) utilised various recruitment strategies. Interventions that recruited participants face-to-face (alone or in combination with other recruitment strategies) (10/15), opportunistic clinic-based screening interventions (5/6) and educational interventions combined with screening (3/4), seemed to be the strategies that consistently achieved an uptake of > 65% in LMICs. FOBT/FIT and colonoscopy uptake ranged between 14 and 100%. The most commonly reported implementation indicator was 'uptake/reach'. There was an absence of detail regarding implementation indicators and there is a need to improve reporting practice in order to disseminate learning about how to implement programmes.

    CONCLUSION: Opportunities and challenges for the implementation of CRC screening programmes were related to the reporting of CRC cases and screening, cost-effective screening methods, knowledge about CRC and screening, staff resources and training, infrastructure of the health care system, financial resources, public health campaigns, policy commitment from governments, patient navigation, planning of screening programmes and quality assurance.

  14. Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.
    BMC Cancer, 2021 Sep 14;21(1):1021.
    PMID: 34521387 DOI: 10.1186/s12885-021-08738-z
    BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.

    METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).

    RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving  10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).

    CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

  15. Syafruddin SE, Nazarie WFWM, Moidu NA, Soon BH, Mohtar MA
    BMC Cancer, 2021 Jul 23;21(1):850.
    PMID: 34301218 DOI: 10.1186/s12885-021-08591-0
    BACKGROUND: Glioblastoma multiforme (GBM) is a highly lethal, stage IV brain tumour with a prevalence of approximately 2 per 10,000 people globally. The cell surface proteins or surfaceome serve as information gateway in many oncogenic signalling pathways and are important in modulating cancer phenotypes. Dysregulation in surfaceome expression and activity have been shown to promote tumorigenesis. The expression of GBM surfaceome is a case in point; OMICS screening in a cell-based system identified that this sub-proteome is largely perturbed in GBM. Additionally, since these cell surface proteins have 'direct' access to drugs, they are appealing targets for cancer therapy. However, a comprehensive GBM surfaceome landscape has not been fully defined yet. Thus, this study aimed to define GBM-associated surfaceome genes and identify key cell-surface genes that could potentially be developed as novel GBM biomarkers for therapeutic purposes.

    METHODS: We integrated the RNA-Seq data from TCGA GBM (n = 166) and GTEx normal brain cortex (n = 408) databases to identify the significantly dysregulated surfaceome in GBM. This was followed by an integrative analysis that combines transcriptomics, proteomics and protein-protein interaction network data to prioritize the high-confidence GBM surfaceome signature.

    RESULTS: Of the 2381 significantly dysregulated genes in GBM, 395 genes were classified as surfaceome. Via the integrative analysis, we identified 6 high-confidence GBM molecular signature, HLA-DRA, CD44, SLC1A5, EGFR, ITGB2, PTPRJ, which were significantly upregulated in GBM. The expression of these genes was validated in an independent transcriptomics database, which confirmed their upregulated expression in GBM. Importantly, high expression of CD44, PTPRJ and HLA-DRA is significantly associated with poor disease-free survival. Last, using the Drugbank database, we identified several clinically-approved drugs targeting the GBM molecular signature suggesting potential drug repurposing.

    CONCLUSIONS: In summary, we identified and highlighted the key GBM surface-enriched repertoires that could be biologically relevant in supporting GBM pathogenesis. These genes could be further interrogated experimentally in future studies that could lead to efficient diagnostic/prognostic markers or potential treatment options for GBM.

  16. Chan LC, Kalyanasundram J, Leong SW, Masarudin MJ, Veerakumarasivam A, Yusoff K, et al.
    BMC Cancer, 2021 May 27;21(1):625.
    PMID: 34044804 DOI: 10.1186/s12885-021-08345-y
    BACKGROUND: Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood.

    METHODS: In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR.

    RESULTS: Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV.

    CONCLUSIONS: This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.

  17. Ang YLE, Ho GF, Soo RA, Sundar R, Tan SH, Yong WP, et al.
    BMC Cancer, 2020 Nov 17;20(1):1118.
    PMID: 33203399 DOI: 10.1186/s12885-020-07616-4
    BACKGROUND: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

    METHODS: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS).

    RESULTS: We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38-3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14-1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15-3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51-1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792).

    CONCLUSIONS: The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial.

    TRIAL REGISTRATION: The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

  18. Alhuthali HM, Bradshaw TD, Lim KH, Kam TS, Seedhouse CH
    BMC Cancer, 2020 Jul 07;20(1):629.
    PMID: 32635894 DOI: 10.1186/s12885-020-07119-2
    BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.

    METHODS: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.

    RESULTS: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).

    CONCLUSIONS: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.

  19. Schliemann D, Paramasivam D, Dahlui M, Cardwell CR, Somasundaram S, Ibrahim Tamin NSB, et al.
    BMC Cancer, 2020 Mar 25;20(1):252.
    PMID: 32213173 DOI: 10.1186/s12885-020-06742-3
    BACKGROUND: Colorectal cancer (CRC) cases are detected late in Malaysia similar to most Asian countries. The Be Cancer Alert Campaign (BCAC) was a culturally adapted mass media campaign designed to improve CRC awareness and reduce late detection in Malaysia. The evaluation of the BCAC-CRC aimed to assess campaign reach, campaign impact and health service use.

    METHODS: Participants aged ≥40 years (n = 730) from randomly selected households in Selangor State Malaysia, completed interview-based assessments. Campaign reach was assessed in terms of responses to an adapted questionnaire that was used in evaluations in other countries. The impact of the campaign was assessed in terms of awareness, confidence to detect symptoms and self-efficacy to discuss symptoms with a doctor as captured by the Cancer Awareness Measure (CAM). CAM was administered before-and-after campaign implementation and responses by BCAC recognisers (i.e. participants who recognised one or more of the BCAC television, radio or print advertisements when prompted) and non-recognisers (i.e. participants who did not recognise any of the BCAC advertisements) were compared analytically. Logistic regression analysed comparative differences in cancer awareness by socio-demographic characteristics and recognition of the BCAC materials.

    RESULTS: Over 65% of participants (n = 484) recognised the BCAC-CRC. Campaign-recognisers were significantly more likely to be aware of each CRC symptom at follow-up and were more confident about noticing symptoms (46.9% vs 34.9%, p = 0.018) compared to non-recognisers. There was no difference between groups in terms of self-efficacy to see a doctor about symptoms. Improved symptoms awareness at follow-up was lower for Indians compared to Malays (adjusted odds ratio (OR) 0.53, 95% Confidence Interval (CI): 0.34, 0.83, p = 0.005). Health service use data did not indicate an increase in screening activity during or immediately after the campaign months.

    CONCLUSION: Overall, the findings of the evaluation indicated that the culturally adapted, evidence-based mass media intervention improved CRC symptom awareness among the Malaysian population; and that impact is more likely when a campaign operates a differentiated approach that matches modes of communication to the ethnic and social diversity in a population.

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