Displaying publications 1 - 20 of 1598 in total

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  1. Too CW, Fong KY, Hang G, Sato T, Nyam CQ, Leong SH, et al.
    J Vasc Interv Radiol, 2024 May;35(5):780-789.e1.
    PMID: 38355040 DOI: 10.1016/j.jvir.2024.02.006
    PURPOSE: To validate the sensitivity and specificity of a 3-dimensional (3D) convolutional neural network (CNN) artificial intelligence (AI) software for lung lesion detection and to establish concordance between AI-generated needle paths and those used in actual biopsy procedures.

    MATERIALS AND METHODS: This was a retrospective study using computed tomography (CT) scans from 3 hospitals. Inclusion criteria were scans with 1-5 nodules of diameter ≥5 mm; exclusion criteria were poor-quality scans or those with nodules measuring <5mm in diameter. In the lesion detection phase, 2,147 nodules from 219 scans were used to develop and train the deep learning 3D-CNN to detect lesions. The 3D-CNN was validated with 235 scans (354 lesions) for sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) analysis. In the path planning phase, Bayesian optimization was used to propose possible needle trajectories for lesion biopsy while avoiding vital structures. Software-proposed needle trajectories were compared with actual biopsy path trajectories from intraprocedural CT scans in 150 patients, with a match defined as an angular deviation of <5° between the 2 trajectories.

    RESULTS: The model achieved an overall AUC of 97.4% (95% CI, 96.3%-98.2%) for lesion detection, with mean sensitivity of 93.5% and mean specificity of 93.2%. Among the software-proposed needle trajectories, 85.3% were feasible, with 82% matching actual paths and similar performance between supine and prone/oblique patient orientations (P = .311). The mean angular deviation between matching trajectories was 2.30° (SD ± 1.22); the mean path deviation was 2.94 mm (SD ± 1.60).

    CONCLUSIONS: Segmentation, lesion detection, and path planning for CT-guided lung biopsy using an AI-guided software showed promising results. Future integration with automated robotic systems may pave the way toward fully automated biopsy procedures.

    Matched MeSH terms: Lung Neoplasms/pathology
  2. Lim CCW, Punjabi LS, Bhatia A, Ng QJ, Jevon GP, Aggarwal IM
    Malays J Pathol, 2024 Apr;46(1):91-94.
    PMID: 38682848
    Intraplacental choriocarcinoma is a rare tumour, with approximately 62 reported cases. It may manifest as a spectrum of disease ranging from an incidental lesion diagnosed on routine placental examination to disseminated maternal and/or neonatal disease. In this case series, we presented two rare cases of intraplacental choriocarcinoma with extremely varied clinical presentations. The extremely varied clinical presentations of both patients described in the case series complicated the process of arriving at the diagnosis. In both cases, subsequent investigations showed no maternal or neonatal metastasis, and maternal serum beta-hCG levels downtrended with conservative management. We aim to highlight the importance of performing a detailed physical examination and evaluation of the patient and multidisciplinary management with oncology opinion. A detailed examination of the placenta should also be considered when faced with obstetric complications so that early diagnosis and the required management can be executed in a prompt fashion.
    Matched MeSH terms: Uterine Neoplasms/pathology
  3. Hamidi LR, Saaid R, Samberkar PN, Wong YP, Tan GC
    Malays J Pathol, 2024 Apr;46(1):117-118.
    PMID: 38682853
    No abstract available.
    Matched MeSH terms: Facial Neoplasms/pathology; Mouth Neoplasms/pathology
  4. Muller S, Tilakaratne WM
    Head Neck Pathol, 2022 Mar;16(1):54-62.
    PMID: 35312982 DOI: 10.1007/s12105-021-01402-9
    The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section "Non-neoplastic Lesions", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.
    Matched MeSH terms: Mouth Neoplasms/pathology
  5. Azfaralariff A, Farahfaiqah F, Shahid M, Sanusi SA, Law D, Mohd Isa AR, et al.
    J Ethnopharmacol, 2022 Jan 30;283:114751.
    PMID: 34662662 DOI: 10.1016/j.jep.2021.114751
    ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (MP) herbs, locally known as Kacip Fatimah, are widely used traditionally to improve women's health. The herb is frequently used for gynecological issues such as menstrual problems, facilitating and quickening delivery, post-partum medication, treats flatulence and dysentery, and. MP extracts are thought to aid in the firming and toning of abdominal muscles, tighten breasts and vaginal muscles, and anti-dysmenorrhea. It also was used for the treatment of gonorrhea and hemorrhoids. As MP product has been produced commercially recently, more in-depth studies should be conducted. The presence of numerous active compounds in MP might provide a synergistic effect and potentially offer other health benefits than those already identified and known.

    AIM OF THE STUDY: This study aimed to use a computational target fishing approach to predict the possible therapeutic effect of Marantodes pumilum and evaluated their effectivity.

    MATERIALS AND METHODS: This study involves a computational approach to identify the potential targets by using target fishing. Several databases were used: PubChem database to obtain the chemical structure of interested compounds; Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) server and the SWISSADME web tool to identify and select the compounds having drug-likeness properties; PharmMapper was used to identify top ten target protein of the selected compounds and Online Mendelian Inheritance in Man (OMIM) was used to predict human genetic problems; the gene id of top-10 proteins was obtained from UniProtKB to be analyzed by using GeneMANIA server to check the genes' function and their co-expression; Gene Pathway established by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) of the selected targets were analyzed by using EnrichR server and confirmed by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) version 6.8 and STRING database. All the interaction data was analyzed by Cytoscape version 3.7.2 software. The protein structure of most putative proteins was obtained from the RCSB protein data bank. Thedocking analysis was conducted using PyRx biological software v0.8 and illustrated by BIOVIA Discovery Studio Visualizer version 20.1.0. As a preliminary evaluation, a cell viability assay using Sulforhodamine B was conducted to evaluate the potential of the predicted therapeutic effect.

    RESULTS: It was found that four studied compounds are highly correlated with three proteins: EFGR, CDK2, and ESR1. These proteins are highly associated with cancer pathways, especially breast cancer and prostate cancer. Qualitatively, cell proliferation assay conducted shown that the extract has IC50 of 88.69 μg/ml against MCF-7 and 66.51 μg/ml against MDA-MB-231.

    CONCLUSIONS: Natural herbs are one of the most common forms of complementary and alternative medicine, and they play an important role in disease treatment. The results of this study show that in addition to being used traditionally to maintain women's health, the use of Marantodes pumilum indirectly has the potential to protect against the development of cancer cells, especially breast cancer. Therefore, further research is necessary to confirm the potential of this plant to be used in the development of anti-cancer drugs, especially for breast cancer.

    Matched MeSH terms: Neoplasms/pathology
  6. See MH, Sinnadurai S, Lai LL, Tan KL, Teh MS, Teoh LY, et al.
    Surgery, 2021 12;170(6):1604-1609.
    PMID: 34538341 DOI: 10.1016/j.surg.2021.08.001
    BACKGROUND: Although immediate breast reconstruction is increasingly becoming popular worldwide, evidence from resource-limited settings is scarce. We investigated factors associated with immediate breast reconstruction in a multiethnic, middle-income Asian setting. Short-term surgical complications, timing of initiation of chemotherapy, and survival outcomes were compared between women undergoing mastectomy alone and their counterparts receiving immediate breast reconstruction.

    METHODS: This historical cohort study included women who underwent mastectomy after diagnosis with stage 0 to stage IIIa breast cancer from 2011 to 2015 in a tertiary hospital. Multivariable regression analyses were used to assess factors associated with immediate breast reconstruction and to measure clinical outcomes.

    RESULT: Out of 790 patients with early breast cancer who had undergone mastectomy, only 68 (8.6%) received immediate breast reconstruction. Immediate breast reconstruction was independently associated with younger age at diagnosis, recent calendar years, Chinese ethnicity, higher education level, and invasive ductal carcinomas. Although immediate breast reconstruction was associated with a higher risk of short-term local surgical complications (adjusted odds ratio: 3.58 [95% confidence interval 1.75-7.30]), there were no significant differences in terms of delay in initiation of chemotherapy, 5-year disease-free survival, and 5-year overall survival between both groups in the multivariable analyses.

    CONCLUSION: Although associated with short-term surgical complications, immediate breast reconstruction after mastectomy does not appear to be associated with delays in initiation of chemotherapy, recurrence, or mortality after breast cancer. These findings are valuable in facilitating shared surgical decision-making, improving access to immediate breast reconstruction, and setting priorities for surgical trainings in middle-income settings.

    Matched MeSH terms: Breast Neoplasms/pathology
  7. Chan VW, Tan WS, Leow JJ, Tan WP, Ong WLK, Chiu PK, et al.
    World J Urol, 2021 Dec;39(12):4295-4303.
    PMID: 34031748 DOI: 10.1007/s00345-021-03734-1
    PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era.

    METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared.

    RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p 

    Matched MeSH terms: Kidney Neoplasms/pathology
  8. Ernst B, Setayesh T, Nersesyan A, Kundi M, Fenech M, Bolognesi C, et al.
    Sci Rep, 2021 11 26;11(1):23014.
    PMID: 34836993 DOI: 10.1038/s41598-021-01995-9
    Consumption of very hot beverages and foods increases the incidence of oral and esophageal cancer but the mechanisms are not known and the critical temperature is not well defined. We realized a study with exfoliated cells from the oral cavity of individuals (n = 73) that live in an area in Iran which has the highest incidence of EC worldwide. Consumption of beverages at very high temperatures is a characteristic feature of this population. We analyzed biomarkers which are (i) indicative for genetic instability (micronuclei that are formed as a consequence of chromosomal damage, nuclear buds which are a consequence of gene amplifications and binucleated cells which reflect mitotic disturbances), (ii) markers that reflect cytotoxic effects (condensed chromatin, karyorrhectic, karyolitic and pyknotic cells), (iii) furthermore, we determined the number of basal cells which is indicative for the regenerative capacity of the buccal mucosa. The impact of the drinking temperature on the frequencies of these parameters was monitored with thermometers. We found no evidence for induction of genetic damage but an increase of the cytotoxic effects with the temperature was evident. This effect was paralleled by an increase of the cell division rate of the mucosa which was observed when the temperature exceeded 60 °C. Our findings indicate that cancer in the upper digestive tract in drinkers of very hot beverages is not caused by damage of the genetic material but by an increase of the cell division rate as a consequence of cytotoxic effects which take place at temperatures over 60 °C. It is known from earlier experiments with rodents that increased cell divisions lead to tumor promotion in the esophagus. Our findings provide a mechanistic explanation and indicate that increased cancer risks can be expected when the drinking temperature of beverages exceeds 60 °C.
    Matched MeSH terms: Esophageal Neoplasms/pathology; Mouth Neoplasms/pathology
  9. Hasbullah HH, Musa M
    Int J Mol Sci, 2021 Nov 03;22(21).
    PMID: 34769370 DOI: 10.3390/ijms222111941
    Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment for CRC, the majority of cases are still being diagnosed at the advanced stage. This contributes to low survivability due to this cancer. CRC patients present various genetic changes and epigenetic modifications. The most common genetic alterations associated with CRC are p53 and KRAS mutations. Gene therapy targeting defect genes such as TP53 (tumor suppressor gene encodes for p53) and KRAS (oncogene) in CRC potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy. For the last decade, significant developments have been seen in gene therapy for translational purposes in treating various cancers. This includes the development of vectors as delivery vehicles. Despite the optimism revolving around targeted gene therapy for cancer treatment, it also has various limitations, such as a lack of availability of related technology, high cost of the involved procedures, and ethical issues. This article will provide a review on the potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  10. Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  11. Poh Yen K, Stanslas J, Zhang T, Li H, Wang X, Kok Meng C, et al.
    Bioorg Med Chem, 2021 11 01;49:116442.
    PMID: 34600241 DOI: 10.1016/j.bmc.2021.116442
    Acquired paclitaxel (PTX) chemoresistance in triple-negative breast cancer (TNBC) can be inferred from the overexpression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) proteins and the activation of the TLR4/MyD88 cascading signalling pathway. Finding a new inhibitor that can attenuate the activation of this pathway is a novel strategy for reducing PTX chemoresistance. In this study, a series of small molecule compounds were synthesised and tested in combination with PTX against TNBC cells. The trimethoxy-substituted compound significantly decreased MyD88 overexpression and improved PTX activity in MDA-MB-231TLR4+ cells but not in HCCTLR4- cells. On the contrary, the trifluoromethyl-substituted compound with PTX synergistically improved the growth inhibition in both TNBC subtypes. The fluorescence titrations indicated that both compounds could bind with MD2 with good and comparable binding affinities. This was further supported by docking analysis, in which both compounds fit perfectly well and form some critical binding interactions with MD2, an essential lipid-binding accessory to TLR4 involved in activating the TLR-4/MyD88-dependent pathway.
    Matched MeSH terms: Triple Negative Breast Neoplasms/pathology
  12. Guerra GR, Kong JC, Millen RM, Read M, Liu DS, Roth S, et al.
    Cell Death Dis, 2021 Oct 18;12(11):959.
    PMID: 34663790 DOI: 10.1038/s41419-021-04141-5
    Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.
    Matched MeSH terms: Anus Neoplasms/pathology*
  13. Prime SS, Cirillo N, Cheong SC, Prime MS, Parkinson EK
    Cancer Lett, 2021 10 10;518:102-114.
    PMID: 34139286 DOI: 10.1016/j.canlet.2021.05.025
    This study reviews the molecular landscape of oral potentially malignant disorders (OPMD). We examine the impact of tumour heterogeneity, the spectrum of driver mutations (TP53, CDKN2A, TERT, NOTCH1, AJUBA, PIK3CA, CASP8) and gene transcription on tumour progression. We comment on how some of these mutations impact cellular senescence, field cancerization and cancer stem cells. We propose that OPMD can be monitored more closely and more dynamically through the use of liquid biopsies using an appropriate biomarker of transformation. We describe new gene interactions through the use of a systems biology approach and we highlight some of the first studies to identify functional genes using CRISPR-Cas9 technology. We believe that this information has translational implications for the use of re-purposed existing drugs and/or new drug development. Further, we argue that the use of digital technology encompassing clinical and laboratory-based data will create relevant datasets for machine learning/artificial intelligence. We believe that therapeutic intervention at an early molecular premalignant stage should be an important preventative strategy to inhibit the development of oral squamous cell carcinoma and that this approach is applicable to other aerodigestive tract cancers.
    Matched MeSH terms: Mouth Neoplasms/pathology
  14. Yang CL, Chao YJ, Wang HC, Hou YC, Chen CG, Chang CC, et al.
    Nanomedicine, 2021 10;37:102450.
    PMID: 34332115 DOI: 10.1016/j.nano.2021.102450
    Epigenetic inhibitors have shown anticancer effects. Combination chemotherapy with epigenetic inhibitors has shown high effectiveness in gastric cancer clinical trials, but severe side effect and local progression are the causes of treatment failure. Therefore, we sought to develop an acidity-sensitive drug delivery system to release drugs locally to diminish unfavorable outcome of gastric cancer. In this study, we showed that, as compared with single agents, combination treatment with the demethylating agent 5'-aza-2'-deoxycytidine and HDAC inhibitors Trichostatin A or LBH589 decreased cell survival, blocked cell cycle by reducing number of S-phase cells and expression of cyclins, increased cell apoptosis by inducing expression of Bim and cleaved Caspase 3, and reexpressed tumor suppressor genes more effectively in MGCC3I cells. As a carrier, reconstituted apolipoprotein B lipoparticles (rABLs) could release drugs in acidic environments. Orally administrated embedded drugs not only showed inhibitory effects on gastric tumor growth in a syngeneic orthotopic mouse model, but also reduced the hepatic and renal toxicity. In conclusion, we have established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which have good therapeutic effects but do not cause severe side effects.
    Matched MeSH terms: Stomach Neoplasms/pathology
  15. Abdullah NA, Inman M, Moody CJ, Storr SJ, Martin SG
    Invest New Drugs, 2021 10;39(5):1232-1241.
    PMID: 33768386 DOI: 10.1007/s10637-021-01106-5
    Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20-1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A.
    Matched MeSH terms: Breast Neoplasms/pathology*; Triple Negative Breast Neoplasms/pathology
  16. Mohd Nafis NS, Mat Zin AA
    Asian Pac J Cancer Prev, 2021 Oct 01;22(10):3261-3266.
    PMID: 34711003 DOI: 10.31557/APJCP.2021.22.10.3261
    Liquid-based preparation (LBP) cytology is commonly used in most laboratories these days due to its convenience and reliable results for the cervical cancer screening program. The PathTezt™ Liquid-based Pap smear is a second-generation LBP, which uses a filter-based concentration technique in processing the sample.

    OBJECTIVE: This study was done to evaluate the cellular fixation, morphology, quality of smear in gynae cytology, and diagnostic interpretation of cervical cytological smears produced by the PathTezt liquid-based processor.

    MATERIALS AND METHODS: A total of 400 pap smear samples were taken and processed using the PathTezt 2000 processor. The slides were evaluated in terms of sample adequacy, percentage of the circle covered by epithelial cells, cellular distribution, obscuring factors, and cell fixation.

    RESULTS: About 95.25% (381) of the samples were satisfactory for the evaluation. In 19 (4.75%) of the samples, epithelial cells covered less than 50% of the circle. A sample with good cellular distribution was seen in 92% of the cases, while 354 (88.5%) samples showed minimal inflammatory background. Almost all the smears (95.75%) had no erythrocytes in the background. All smears showed good quality fixation features toward nuclear, cytoplasm, and microorganisms. The total performance rate was 99%.

    CONCLUSION: Although the PathTezt liquid-based processor is still new compared to other first-generation LBP, the smears produced by this method were of high quality and it was cost-effective.

    Matched MeSH terms: Uterine Cervical Neoplasms/pathology*
  17. Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, et al.
    J Pediatr Hematol Oncol, 2021 Oct 01;43(7):e913-e923.
    PMID: 33633029 DOI: 10.1097/MPH.0000000000002116
    BACKGROUND: A higher incidence of pediatric intracranial germ cell tumors (iGCTs) in Asian countries compared with Western countries has been reported. In Malaysia, the literature regarding pediatric iGCTs have been nonexistent. The aim of this study was to review the management, survival, and long-term outcomes of pediatric iGCTs at a single tertiary center in Malaysia.

    PATIENTS AND METHODS: We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017.

    RESULTS: Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status.

    CONCLUSIONS: The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.

    Matched MeSH terms: Brain Neoplasms/pathology
  18. Juhari WKW, Ahmad Amin Noordin KB, Zakaria AD, Rahman WFWA, Mokhter WMMWM, Hassan MRA, et al.
    Genes (Basel), 2021 09 20;12(9).
    PMID: 34573430 DOI: 10.3390/genes12091448
    BACKGROUND: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.

    METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.

    RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.

    CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  19. 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.

    Matched MeSH terms: Kidney Neoplasms/pathology
  20. Maniam S, Maniam S
    Int J Mol Sci, 2021 Sep 08;22(18).
    PMID: 34575883 DOI: 10.3390/ijms22189722
    Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.
    Matched MeSH terms: Breast Neoplasms/pathology
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