Displaying publications 1 - 20 of 58 in total

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  1. Ismail R, Allaudin ZN, Abdullah R, Mohd Lila MA, Nik Abd Rahman NM, Abdul Rahman SO
    BMC Cancer, 2016 07 13;16:461.
    PMID: 27411985 DOI: 10.1186/s12885-016-2530-8
    BACKGROUND: Cancer therapies that kill cancer cells without affecting normal cells is the ultimate mode of treating cancers. The VP3, an avian virus-derived protein, can specifically initiate cell death through several signal transduction pathways leading to apoptosis. In cancer, chemoresistance and cell survivability implicate the cell surface protein, CD147.

    METHODS: In this study, transfection of VP3 and silencing of CD147 genes was achieved through the treatment of tumors with pVIVO1-GFP/VP3 (VP3), psiRNA-CD147/2 (shCD147/2), and their combination of CT26 colon cancer cell-induced in mice. The effectiveness of tumor-treatment was ascertained by electrophoresis, TUNEL assay, and flow cytometry analysis. While histopathological and biochemical analysis were used as toxic side effect identification.

    RESULTS: The tumor growth delay index (TGDI) after treatment with VP3, shCD147/2, and their combination treatments increased by 1.3-, 1.2-, 2.0- and 2.3-fold respectively, over untreated control. The VP3-shCD147/2 combination treatment was more efficacious then either VP3 or shCD147/2 alone in the retardation of mouse CT26 colorectal cell tumor allograft.

    CONCLUSION: The antitumor effect of the combination treatment is the result of synergistic effects of VP3 and shCD147/2 on the tumor cells resulting in apoptosis. Thus, the study shows that combination of VP3 and shCD147/2 treatment can be developed into a potential approach for anticolorectal cancer treatment regimen.

  2. Abdulamir AS, Hafidh RR, Mahdi LK, Al-jeboori T, Abubaker F
    BMC Cancer, 2009;9:403.
    PMID: 19925668 DOI: 10.1186/1471-2407-9-403
    The seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-kappaB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis.
  3. Al-Khayal K, Alafeefy A, Vaali-Mohammed MA, Mahmood A, Zubaidi A, Al-Obeed O, et al.
    BMC Cancer, 2017 01 03;17(1):4.
    PMID: 28049506 DOI: 10.1186/s12885-016-3005-7
    BACKGROUND: Colorectal cancer (CRC) is the 3(rd) most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown.

    METHODS: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29.

    RESULTS: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3.

    CONCLUSIONS: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.

  4. Chua LL, Rajasuriar R, Lim YAL, Woo YL, Loke P, Ariffin H
    BMC Cancer, 2020 Feb 24;20(1):151.
    PMID: 32093640 DOI: 10.1186/s12885-020-6654-5
    BACKGROUND: Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.

    METHODOLOGY: We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.

    RESULTS: Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.

    CONCLUSION: Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

  5. Oh L, Hainaut P, Blanchet S, Ariffin H
    BMC Cancer, 2020 Feb 10;20(1):110.
    PMID: 32041553 DOI: 10.1186/s12885-020-6599-8
    BACKGROUND: TP53 mutations occur in only about 3% of primary and 10-20% of relapse B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). However, alternative mechanisms may contribute to functionally impairing the p53 pathway in the absence of a mutation. Candidate mechanisms include overexpression of p53 mRNA variants encoding either dominant-negative p53 protein isoforms such as Delta40p53 and Delta133p53, or modulatory isoforms such as p53beta, which counteract the effects of Delta133p53 on replicative senescence in T-lymphocytes.

    METHODS: We used semi-quantitative reverse-transcriptase PCR (RT-PCR) and Western blot to investigate the expression of full length p53 (TAp53), Delta40p53, Delta133p53 or p53beta in diagnostic marrow from a clinical cohort of 50 BCP-ALL patients without TP53 mutation (29 males and 21 females, age range 2-14 years) and in the bone marrow cells of 4 healthy donors (used as controls).

    RESULTS: Irrespective of isoforms, levels of p53 mRNA were low in controls but were increased by 2 to 20-fold in primary or relapse BCP-ALL. TAp53 was increased in primary BCP-ALL, Delta40p53 was elevated in relapse BCP-ALL, whereas Delta133p53 and p53beta were increased in both. Next, mRNA levels were used as a basis to infer the ratio between protein isoform levels. This inference suggested that, in primary BCP-ALL, p53 was predominantly in active oligomeric conformations dominated by TAp53. In contrast, p53 mostly existed in inactive quaternary conformations containing ≥2 Delta40 or Delta133p53 in relapse BCP-ALL. Western blot analysis of blasts from BCP-ALL showed a complex pattern of N-terminally truncated p53 isoforms, whereas TAp53beta was detected as a major isoform. The hypothesis that p53 is in an active form in primary B-ALL was consistent with elevated level of p53 target genes CDKN1A and MDM2 in primary cases, whereas in relapse BCP-ALL, only CDKN1A was increased as compared to controls.

    CONCLUSION: Expression of p53 isoforms is deregulated in BCP-ALL in the absence of TP53 mutation, with increased expression of alternative isoforms in relapse BCP-ALL. Variations in isoform expression may contribute to functional deregulation of the p53 pathway in BCP-ALL, specifically contributing to its down-regulation in relapse forms.

  6. 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).

  7. Miao H, Hartman M, Verkooijen HM, Taib NA, Wong HS, Subramaniam S, et al.
    BMC Cancer, 2016 10 21;16(1):820.
    PMID: 27769212
    BACKGROUND: CancerMath is a set of web-based prognostic tools which predict nodal status and survival up to 15 years after diagnosis of breast cancer. This study validated its performance in a Southeast Asian setting.

    METHODS: Using Singapore Malaysia Hospital-Based Breast Cancer Registry, clinical information was retrieved from 7064 stage I to III breast cancer patients who were diagnosed between 1990 and 2011 and underwent surgery. Predicted and observed probabilities of positive nodes and survival were compared for each subgroup. Calibration was assessed by plotting observed value against predicted value for each decile of the predicted value. Discrimination was evaluated by area under a receiver operating characteristic curve (AUC) with 95 % confidence interval (CI).

    RESULTS: The median predicted probability of positive lymph nodes is 40.6 % which was lower than the observed 43.6 % (95 % CI, 42.5 %-44.8 %). The calibration plot showed underestimation for most of the groups. The AUC was 0.71 (95 % CI, 0.70-0.72). Cancermath predicted and observed overall survival probabilities were 87.3 % vs 83.4 % at 5 years after diagnosis and 75.3 % vs 70.4 % at 10 years after diagnosis. The difference was smaller for patients from Singapore, patients diagnosed more recently and patients with favorable tumor characteristics. Calibration plot also illustrated overprediction of survival for patients with poor prognosis. The AUC for 5-year and 10-year overall survival was 0.77 (95 % CI: 0.75-0.79) and 0.74 (95 % CI: 0.71-0.76).

    CONCLUSIONS: The discrimination and calibration of CancerMath were modest. The results suggest that clinical application of CancerMath should be limited to patients with better prognostic profile.

  8. Norsa'adah B, Rampal KG, Rahmah MA, Naing NN, Biswal BM
    BMC Cancer, 2011;11:141.
    PMID: 21496310 DOI: 10.1186/1471-2407-11-141
    Breast cancer is the leading cause of cancer mortality among women in Malaysia. Delayed diagnosis is preventable and has major effects on patients' prognosis and survival. The objectives of our study were to identify the magnitude of delayed diagnosis and its associated factors in women with breast cancer in Malaysia.
  9. Veettil SK, Lim KG, Ching SM, Saokaew S, Phisalprapa P, Chaiyakunapruk N
    BMC Cancer, 2017 Nov 14;17(1):763.
    PMID: 29137605 DOI: 10.1186/s12885-017-3757-8
    BACKGROUND: Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established.

    METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).

    RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.

    CONCLUSION: Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

  10. Sim X, Ali RA, Wedren S, Goh DL, Tan CS, Reilly M, et al.
    BMC Cancer, 2006;6:261.
    PMID: 17078893
    From 1968 to 2002, Singapore experienced an almost three-fold increase in breast cancer incidence. This increase appeared to be different across the three main ethnic groups: Chinese, Malays and Indians. This paper used age-period-cohort (APC) modelling, to determine the effects of age at diagnosis, calendar period, and birth cohort on breast cancer incidence for each ethnic group.
  11. 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.

  12. Kaniappan K, Lim CTS, Chin PW
    BMC Cancer, 2018 Aug 02;18(1):779.
    PMID: 30068299 DOI: 10.1186/s12885-018-4702-1
    BACKGROUND: Cases of non-traumatic splenic rupture are rare and entails a potentially grave medical outcome. Hence, it is important to consider the differential diagnosis of a non-traumatic splenic rupture in patients with acute or insidious abdominal pain. The incidence of rupture in Diffuse B-cell non-Hodgkin Lymphoma is highly infrequent (Paulvannan and Pye, Int J Clin Pract 57:245-6, 2003; Gedik et el., World J Gastroenterol 14:6711-6716, 2008), despite reports of various non-traumatic splenic rupture in the literature (Orloff and Peksin, Int Abstr Surg 106:1-11, 1958; Paulvannan and Pye, Int J Clin Pract 57:245-6, 2003). In this article, we attempt to highlight the features of a rare cause of splenic rupture that might serve as a future reference point for the detection of similar cases during routine clinical practice.

    CASE PRESENTATION: A 40-year-old man presented with 1 week history of left hypochondriac pain associated with abdominal distention. There was no history of preceding trauma or fever. Clinical examination revealed signs of tachycardia, pallor and splenomegaly. He had no evidence of peripheral stigmata of chronic liver disease. In addition, haematological investigation showed anemia with leucocytosis and raised levels of lactate dehydrogenase enzyme. However, peripheral blood film revealed no evidence of any blast or atypical cells. In view of these findings, imaging via ultrasound and computed tomography of the abdomen was performed. The results of these imaging tests showed splenic collections that was suggestive of splenic rupture and hematoma. Patient underwent emergency splenectomy and the histopathological report confirmed the diagnosis as DLBCL.

    CONCLUSIONS: The occurrence of true spontaneous splenic rupture is uncommon. In a recent systematic review of 613 cases of splenic rupture, only 84 cases were secondary to hematological malignancy. Acute leukemia and non-Hodgkin lymphoma were the most frequent causes of splenic rupture, followed by chronic and acute myelogeneous leukemias. At present, only a few cases of diffuse large B-cell lymphoma (DLBCL) have been reported. The morbidity and mortality rate is greatly increased when there is a delay in the diagnosis and intervention of splenic rupture cases. Hence, there should be an increased awareness amongst both physicians and surgeons that a non-traumatic splenic rupture could be the first clinical presentation of a DLBCL.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Lim GC, Aina EN, Cheah SK, Ismail F, Ho GF, Tho LM, et al.
    BMC Cancer, 2014;14:212.
    PMID: 24650245 DOI: 10.1186/1471-2407-14-212
    BACKGROUND: Cancer is the leading cause of deaths in the world. A widening disparity in cancer burden has emerged between high income and low-middle income countries. Closing this cancer divide is an ethical imperative but there is a dearth of data on cancer services from developing countries.
    METHODS: This was a multi-center, retrospective observational cohort study which enrolled women with breast cancer (BC) attending 8 participating cancer centers in Malaysia in 2011. All patients were followed up for 12 months from diagnosis to determine their access to therapies. We assess care performance using measures developed by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comprehensive Cancer Network, American College of Surgeons' National Accreditation Program for Breast Centers as well as our local guideline.
    RESULTS: Seven hundred and fifty seven patients were included in the study; they represent about 20% of incident BC in Malaysia. Performance results were mixed. Late presentation was 40%. Access to diagnostic and breast surgery services were timely; the interval from presentation to tissue diagnosis was short (median = 9 days), and all who needed surgery could receive it with only a short wait (median = 11 days). Performance of radiation, chemo and hormonal therapy services showed that about 75 to 80% of patients could access these treatments timely, and those who could not were because they sought alternative treatment or they refused treatment. Access to Trastuzumab was limited to only 19% of eligible patients.
    CONCLUSIONS: These performance results are probably acceptable for a middle income country though far below the 95% or higher adherence rates routinely reported by centres in developed countries. High cost trastuzumab was inaccessible to this population without public funding support.
  20. Salmasi S, Lee KS, Ming LC, Neoh CF, Elrggal ME, Babar ZD, et al.
    BMC Cancer, 2017 12 28;17(1):903.
    PMID: 29282008 DOI: 10.1186/s12885-017-3888-y
    BACKGROUND: Globally, cancer is one of the leading causes of mortality. High treatment cost, partly owing to higher prices of anti-cancer drugs, presents a significant burden on patients and healthcare systems. The aim of the present study was to survey and compare retail prices of anti-cancer drugs between high, middle and low income countries in the South-East Asia, Western Pacific and Eastern Mediterranean regions.

    METHODS: Cross-sectional survey design was used for the present study. Pricing data from ten counties including one from South-East Asia, two from Western Pacific and seven from Eastern Mediterranean regions were used in this study. Purchasing power parity (PPP)-adjusted mean unit prices for 26 anti-cancer drug presentations (similar pharmaceutical form, strength, and pack size) were used to compare prices of anti-cancer drugs across three regions. A structured form was used to extract relevant data. Data were entered and analysed using Microsoft Excel®.

    RESULTS: Overall, Taiwan had the lowest mean unit prices while Oman had the highest prices. Six (23.1%) and nine (34.6%) drug presentations had a mean unit price below US$100 and between US$100 and US$500 respectively. Eight drug presentations (30.7%) had a mean unit price of more than US$1000 including cabazitaxel with a mean unit price of $17,304.9/vial. There was a direct relationship between income category of the countries and their mean unit price; low-income countries had lower mean unit prices. The average PPP-adjusted unit prices for countries based on their income level were as follows: low middle-income countries (LMICs): US$814.07; high middle income countries (HMICs): US$1150.63; and high income countries (HICs): US$1148.19.

    CONCLUSIONS: There is a great variation in pricing of anticancer drugs in selected countires and within their respective regions. These findings will allow policy makers to compare prices of anti-cancer agents with neighbouring countries and develop policies to ensure accessibility and affordability of anti-cancer drugs.

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