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Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells

Basar N, Oridupa OA, Ritchie KJ, Nahar L, Osman NM, Stafford A, et al.

Phytother Res, 2015 Jun;29(6):944-8.
PMID: 25779384 DOI: 10.1002/ptr.5329

Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra.

Matched MeSH terms: Liver Neoplasms/pathology; Lung Neoplasms/pathology
Rhabdomyosarcoma of the middle ear and mastoid in children

Said H, Phang KS, Razi A, Khuzaiyah R, Patawari PH, Esa R

J Laryngol Otol, 1988 Jul;102(7):614-9.
PMID: 3411216

Three cases of embryonal rhabdomyosarcoma in the middle ear and mastoid in children are presented. Diagnosis was confirmed by histopathology. A multidisciplinary approach employing surgery, chemotherapy and radiation therapy is the method of choice in the management of this rare and highly lethal condition.

Matched MeSH terms: Ear Neoplasms/pathology*; Skull Neoplasms/pathology*
Malignant obstruction of superior vena cava: Endovascular stenting using Y-configuration stent in stent technique

Noor Khairiah AK, Mohamad Nazrulhisham MN, Hazman MN

Med J Malaysia, 2018 12;73(6):407-409.
PMID: 30647215

Malignant intrathoracic disease is the commonest cause of superior vena cava (SVC) obstruction. Life threatening SVC obstruction with intense dyspnoea requires urgent treatment. SVC stenting has been developed in recent years which results in rapid relief of the obstruction. The Yconfiguration technique has been reported to provide support for all three limbs of the bifurcation to prevent restenosis. At present, there are limited reports on the use of Y-configuration stent in stent techniques for endovascular stenting in malignant SVC obstruction. We share our clinical experience of two patients who received balloon-mounted stents using this technique.

Matched MeSH terms: Uterine Cervical Neoplasms/pathology; Lung Neoplasms/pathology
Cutaneous metastasis of hepatocellular carcinoma diagnosed by fine needle aspiration cytology and Hep Par 1 immunopositivity

Isa NM, Bong JJ, Ghani FA, Rose IM, Husain S, Azrif M

Diagn Cytopathol, 2012 Nov;40(11):1010-4.
PMID: 21563319 DOI: 10.1002/dc.21706

Cutaneous metastasis of hepatocellular carcinoma (HCC) is very rare, accounting for less than 0.8% of all known cutaneous metastases and occurring in 2.7-3.4% of HCCs. With less than 50 such cases reported worldwide, most of which were diagnosed histologically on excised lesions, it can only be expected that diagnosis made on cytological features alone would be challenging. We report a case of cutaneous metastasis of HCC diagnosed based on cytological features and confirmed by Hep Par 1 immunopositivity of the cell block material. An 81-year-old man, who was known to have unresectable HCC, presented with a 1-month history of painless, left nasal alae mass. The mass measured 1.5 cm in diameter, and was multilobulated with a central necrosis. Fine needle aspiration of the mass was done. Smears were cellular, comprising of malignant cells in loose clusters and aggregates as well as singly dispersed. The malignant cells displayed moderate nuclear pleomorphism, occasional prominent nucleoli, and intranuclear pseudoinclusion. Cell block material demonstrated the trabeculae pattern of the malignant cells and Hep Par 1 immunopositivity. The final diagnosis of a metastatic cutaneous HCC was made. In conclusion, cutaneous HCC metastasis is rare and should be considered in the differential diagnosis in patients with a history of HCC presenting with suspicious skin lesion. In the right clinical setting, a confident diagnosis can be made in such cases by using the fine needle aspiration technique aided with immunopositivity for Hep Par 1 antibody of the aspirated material.

Matched MeSH terms: Liver Neoplasms/pathology; Nose Neoplasms/pathology
Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells

Halder A, Jethwa M, Mukherjee P, Ghosh S, Das S, Helal Uddin ABM, et al.

Artif Cells Nanomed Biotechnol, 2020 Nov 17;48(1):1362-1371.
PMID: 33284038 DOI: 10.1080/21691401.2020.1850465

Cancer management presents multifarious problems. Triple negative breast cancer (TNBC) is associated with inaccurate prognosis and limited chemotherapeutic options. Betulinic acid (BA) prevents angiogenesis and causes apoptosis of TNBC cells. NIH recommends BA for rapid access in cancer chemotherapy because of its cell-specific toxicity. BA however faces major challenges in therapeutic practices due to its limited solubility and cellular entree. We report lactoferrin (Lf) attached BA nanoparticles (Lf-BAnp) for rapid delivery in triple negative breast (MDA-MB-231) and laryngeal (HEp-2) cancer cell types. Lf association was confirmed by SDS-PAGE and FT-IR analysis. Average hydrodynamic size of Lf-BAnp was 147.7 ± 6.20 nm with ζ potential of -28.51 ± 3.52 mV. BA entrapment efficiency was 75.38 ± 2.70% and the release mechanism followed non-fickian pattern. Impact of Lf-BAnp on cell cycle and cytotoxicity of triple negative breast cancer and its metastatic site laryngeal cancer cell lines were analyzed. Lf-BAnp demonstrated strong anti-proliferative and cytotoxic effects, along with increased sub-G1 population and reduced number of cells in G1 and G2/M phases of the cell cycle, confirming reduced cell proliferation and significant cell death. Speedy intracellular entry of Lf-BAnp occurred within 30 min. Lf-BAnp design was explored for the first time as safer chemotherapeutic arsenals against complex TNBC conditions.

Matched MeSH terms: Laryngeal Neoplasms/pathology*; Triple Negative Breast Neoplasms/pathology*
Comparative assessment of urinary oxidative indices in breast and colorectal cancer patients

Chandramathi S, Suresh K, Anita ZB, Kuppusamy UR

J Cancer Res Clin Oncol, 2009 Feb;135(2):319-23.
PMID: 18758816 DOI: 10.1007/s00432-008-0462-7

PURPOSE: This study aimed to use non-invasive methods to assess and compare the levels of oxidative indices and non-enzymatic antioxidants in breast and colorectal cancer (CRC) patients. Various studies have reported on lipid peroxidation, hydrogen peroxide (H(2)O(2)) and ferric-reducing antioxidant power (FRAP) levels in the serum of cancer patients but this is the first report that highlights the significance of urinary-advanced oxidative protein product (AOPP) in cancer patients.
METHODS: The levels of advanced oxidative protein product (AOPP), hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA) which is a marker for lipid peroxidation and ferric-reducing antioxidant power (FRAP) were measured in urine samples of breast (n = 101) and colorectal cancer (n = 49) patients attending the Oncology Clinic, University Malaya Medical Centre, Kuala Lumpur and were compared with 95 age-matched healthy individuals.
RESULTS: AOPP, H(2)O(2) and MDA levels in the urine were significantly higher in the CRC patients compared to the control subjects and breast cancer patients. In breast cancer patients, only AOPP level was elevated. FRAP level did not differ between breast and colorectal cancer patients but the levels were significantly lower compared to control subjects.
CONCLUSION: Urinary oxidative indices such as AOPP, H(2)O(2), and MDA as well as FRAP could serve as useful non-invasive oxidative stress markers in colorectal cancer but only AOPP serves as a useful urinary oxidative biomarker in breast cancer.
Study site: Oncology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Breast Neoplasms/pathology; Colorectal Neoplasms/pathology
Roles of MicroRNA21 and MicroRNA29a in Regulating Cell Adhesion Related Genes in Bone Metastasis Secondary to Prostate Cancer

Mohamad M, Wahab NA, Yunus R, Murad NA, Zainuddin ZM, Sundaram M, et al.

Asian Pac J Cancer Prev, 2016;17(7):3437-45.
PMID: 27509989

BACKGROUND: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be downregulated in clinical samples, most likely due to the posttranscriptional modification by microRNAs. Targeted genes would be upregulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors.
MATERIALS AND METHODS: MicroRNA software predicted that miR21 targets VCL while miR29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalinfixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels.
RESULTS: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down regulated while CX3CL1 was upregulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly up regulated while CX3CL1 mRNA was significantly downregulated compared to the RWPE1 case.
CONCLUSIONS: The downregulation of VCL in FFPE specimens is most likely regulated by miR21 based on the in vitro evidence but the exact mechanism of how miR21 can regulate VCL is unclear. Upregulated in CaP, CX3CL1 was found not regulated by miR29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNAmRNA interactions may provide additional knowledge for individualized study of cancers.

Matched MeSH terms: Bone Neoplasms/pathology; Prostatic Neoplasms/pathology
Metastatic Pleomorphic Adenoma in the infratemporal fossa and neck following total parotidectomy after 30 years

Wong DKC, Muhamad NS, Sobri SS, Amin WAM, Yusof Z

Med J Malaysia, 2019 04;74(2):85-86.
PMID: 31079134

Metastasising pleomorphic adenoma is rare and may occur years after surgical excision of a pleomorphic adenoma (PA). We present a 61-year-old woman with a right infratemporal PA with metastases to the cervical lymph nodes after 30 years following a total parotidectomy. She was treated successfully with a resection of the tumour with combined neck and mandibulotomy approach along with postoperative radiotherapy given subsequently.

Matched MeSH terms: Head and Neck Neoplasms/pathology; Skull Base Neoplasms/pathology
Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis

Ramdas P, Radhakrishnan AK, Abdu Sani AA, Abdul-Rahman PS

Nutr Cancer, 2019;71(8):1263-1271.
PMID: 31084432 DOI: 10.1080/01635581.2019.1607407

Tocotrienols (T3), a family of vitamin E, are reported to possess potent anti-cancer effects but the molecular mechanisms behind these effects still remain unclear. The aim of this study was to investigate how T3 exert anti-cancer effects on MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were chosen for this study as they are triple-negative and highly metastatic cells, which form aggressive tumors in experimental models. The MDA-MB-231 cells were treated with varying concentrations (0-20 µg mL-1) of gamma (γ) or delta (δ) T3 and the secretome profiles of these cells treated with half maximal inhibitory concentration (IC50) of γT3 (5.8 µg mL-1) or δT3 (4.0 µg mL-1) were determined using label-free quantitative proteomic strategy. A total of 103, 174 and 141 proteins were identified with ProteinLynx Global Server (PLGS) score of more than 200 and above 25% sequence coverage in the untreated control and T3-treated cell culture supernatant respectively. A total of 18 proteins were dysregulated between untreated control and T3 (δT3 or γT3) treated conditions. The results showed that T3 treatment downregulated the exogenous Cathepsin D and Serpine1 proteins but upregulated Profilin-1 protein, which play a key role in breast cancer in the MDA-MB-231 cells. These findings strongly suggest that T3 may induce differential expression of secreted proteins involved in the cytoskeletal regulation of RHO GTPase signaling pathway.

Matched MeSH terms: Breast Neoplasms/pathology; Triple Negative Breast Neoplasms/pathology
Fulltext Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

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
Fulltext Dopamine-secreting phaeochromocytomas and paragangliomas: clinical features and management

Foo SH, Chan SP, Ananda V, Rajasingam V

Singapore Med J, 2010 May;51(5):e89-93.
PMID: 20593136

Most functional phaeochromocytomas/paragangliomas produce noradrenaline and/or adrenaline. Those that produce dopamine are rare. We describe the distinguishing clinical features of dopamine-secreting phaeochromocytomas and paragangliomas from those that secrete noradrenaline/adrenaline and the impact on their management. We present a case of a dopamine-secreting paraganglioma from our institution and review 14 case reports of dopamine-secreting phaeochromocytomas/paragangliomas published between 1984 and 2008. As observed in the literature, 80% of the tumours were extra-adrenal. Most patients presented with non-specific symptoms or mass effect without the classical presentation of catecholamine excess. The majority were diagnosed with urinary or plasma dopamine. Five patients had malignant tumours and 12 patients underwent surgical resection of the primary tumours. Unlike noradrenaline/adrenaline-secreting phaeochromocytomas/paragangliomas, dopamine-secreting tumours lack a classical presentation, are extra-adrenal and have a higher malignant potential. A routine inclusion of urinary or plasma dopamine as part of catecholamine screening in all suspected phaeochromocytomas and paragangliomas is recommended.

Matched MeSH terms: Abdominal Neoplasms/pathology; Adrenal Gland Neoplasms/pathology
Fulltext Extramedullary plasmacytoma in the maxillary sinus

Megat Shiraz MA, Jong YH, Primuharsa Putra SH

Singapore Med J, 2008 Nov;49(11):e310-1.
PMID: 19037537

Extramedullary plasmacytoma is a rare malignant plasma cell tumour. We report an extremely aggressive case of extramedullary plasmacytoma of the right maxillary sinus, which had metastasised to the brain and rib. A 56-year-old man presented with recurrent epistaxis and acute anaemia. Nasendoscopy revealed a medialised medial wall of the right maxilla and a mass occupying the whole nasopharynx. Magnetic resonance imaging revealed a right maxillary tumour with extension to the ipsilateral nasal cavity, nasopharynx, right sphenoid and ethmoidal sinuses. There was an extra-axial brain metastasis. There were metastases to the right parietal region and left eighth rib. Histopathology examination of the maxillary mass revealed abundant plasma cells with kappa-chain restriction. He was planned for four cycles of chemotherapy. Unfortunately, in view of the advanced stage of disease, he succumbed to his disease during the first cycle of chemotherapy.

Matched MeSH terms: Brain Neoplasms/pathology*; Maxillary Sinus Neoplasms/pathology
Fulltext Investigations concerning the impact of consumption of hot beverages on acute cytotoxic and genotoxic effects in oral mucosa cells

Ernst B, Setayesh T, Nersesyan A, Kundi M, Fenech M, Bolognesi C, et al.

Sci Rep, 2021 Nov 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
Controlled release of doxorubicin from electrospun PEO/chitosan/graphene oxide nanocomposite nanofibrous scaffolds

Ardeshirzadeh B, Anaraki NA, Irani M, Rad LR, Shamshiri S

Mater Sci Eng C Mater Biol Appl, 2015 Mar;48:384-90.
PMID: 25579938 DOI: 10.1016/j.msec.2014.12.039

Polyethylene oxide (PEO)/chitosan (CS)/graphene oxide (GO) electrospun nanofibrous scaffolds were successfully developed via electrospinning process for controlled release of doxorubicin (DOX). The SEM analysis of nanofibrous scaffolds with different contents of GO (0.1, 0.2, 0.5 and 0.7wt.%) indicated that the minimum diameter of nanofibers was found to be 85nm for PEO/CS/GO 0.5% nanofibers. The π-π stacking interaction between DOX and GO with fine pores of nanofibrous scaffolds exhibited higher drug loading (98%) and controlled release of the DOX loaded PEO/CS/GO nanofibers. The results of DOX release from nanofibrous scaffolds at pH5.3 and 7.4 indicated strong pH dependence. The hydrogen bonding interaction between GO and DOX could be unstable under acidic conditions which resulted in faster drug release rate in pH5.3. The cell viability results indicated that DOX loaded PEO/CS/GO/DOX nanofibrous scaffold could be used as an alternative source of DOX compared with free DOX to avoid the side effects of free DOX. Thus, the prepared nanofibrous scaffold offers as a novel formulation for treatment of lung cancer.

Matched MeSH terms: Lung Neoplasms/pathology
Fulltext A novel hybrid classification model of genetic algorithms, modified k-Nearest Neighbor and developed backpropagation neural network

Salari N, Shohaimi S, Najafi F, Nallappan M, Karishnarajah I

PLoS One, 2014;9(11):e112987.
PMID: 25419659 DOI: 10.1371/journal.pone.0112987

Among numerous artificial intelligence approaches, k-Nearest Neighbor algorithms, genetic algorithms, and artificial neural networks are considered as the most common and effective methods in classification problems in numerous studies. In the present study, the results of the implementation of a novel hybrid feature selection-classification model using the above mentioned methods are presented. The purpose is benefitting from the synergies obtained from combining these technologies for the development of classification models. Such a combination creates an opportunity to invest in the strength of each algorithm, and is an approach to make up for their deficiencies. To develop proposed model, with the aim of obtaining the best array of features, first, feature ranking techniques such as the Fisher's discriminant ratio and class separability criteria were used to prioritize features. Second, the obtained results that included arrays of the top-ranked features were used as the initial population of a genetic algorithm to produce optimum arrays of features. Third, using a modified k-Nearest Neighbor method as well as an improved method of backpropagation neural networks, the classification process was advanced based on optimum arrays of the features selected by genetic algorithms. The performance of the proposed model was compared with thirteen well-known classification models based on seven datasets. Furthermore, the statistical analysis was performed using the Friedman test followed by post-hoc tests. The experimental findings indicated that the novel proposed hybrid model resulted in significantly better classification performance compared with all 13 classification methods. Finally, the performance results of the proposed model was benchmarked against the best ones reported as the state-of-the-art classifiers in terms of classification accuracy for the same data sets. The substantial findings of the comprehensive comparative study revealed that performance of the proposed model in terms of classification accuracy is desirable, promising, and competitive to the existing state-of-the-art classification models.

Matched MeSH terms: Breast Neoplasms/pathology
Predictive model of oral cancer metastasis for different cancer sites and age groups

Siriwardena BS, Rasnayaka RM, Masood Y, Masood M, Kumarasiri PV, Tilakaratne WM

J Investig Clin Dent, 2016 May;7(2):127-31.
PMID: 25573428 DOI: 10.1111/jicd.12145

AIM: The high incidence rates for oral cancer (excluding lip) are especially found in the South and South-East Asia. Therefore, the aim of the present study was to investigate the relationship between sex, age, site, and metastasis of a large sample with oral squamous cell carcinoma (OSCC).
METHODS: A total of 989 OSCC treated with neck dissection were selected. All the relevant data were recorded from biopsy request forms. The patients were divided into seven groups, and there were nine different oral sites.
RESULTS: The male-to-female ratio of the sample was 4:1. Most of the patients were aged between 30 and 60 years. Of the 989 patients, approximately 40% patients had metastasis. Age <30 years showed a higher probability of metastasis compared to higher age groups, but it was not statistically significant. Palate cancers had more than 14 times higher chance of metastasis, followed by maxilla (4.6 times) and tongue (2.8 times).
CONCLUSION: The present study provides important information on the metastatic potential of OSCC in different oral sites, and identifies high-risk age groups for metastasis. This will be helpful in planning neck treatment for OSCC.

Matched MeSH terms: Mouth Neoplasms/pathology*
The kinase LMTK3 promotes invasion in breast cancer through GRB2-mediated induction of integrin β₁

Xu Y, Zhang H, Lit LC, Grothey A, Athanasiadou M, Kiritsi M, et al.

Sci Signal, 2014 Jun 17;7(330):ra58.
PMID: 24939894 DOI: 10.1126/scisignal.2005170

Lemur tyrosine kinase 3 (LMTK3) is associated with cell proliferation and endocrine resistance in breast cancer. We found that, in cultured breast cancer cell lines, LMTK3 promotes the development of a metastatic phenotype by inducing the expression of genes encoding integrin subunits. Invasive behavior in various breast cancer cell lines positively correlated with the abundance of LMTK3. Overexpression of LMTK3 in a breast cancer cell line with low endogenous LMTK3 abundance promoted actin cytoskeleton remodeling, focal adhesion formation, and adhesion to collagen and fibronectin in culture. Using SILAC (stable isotope labeling by amino acids in cell culture) proteomic analysis, we found that LMTK3 increased the abundance of integrin subunits α5 and β1, encoded by ITGA5 and ITGB1. This effect depended on the CDC42 Rho family guanosine triphosphatase, which was in turn activated by the interaction between LMTK3 and growth factor receptor-bound protein 2 (GRB2), an adaptor protein that mediates receptor tyrosine kinase-induced activation of RAS and downstream signaling. Knockdown of GRB2 suppressed LMTK3-induced CDC42 activation, blocked ITGA5 and ITGB1 expression promoted by the transcription factor serum response factor (SRF), and reduced invasive activity. Furthermore, abundance of LMTK3 positively correlated with that of the integrin β1 subunit in breast cancer patient's tumors. Our findings suggest a role for LMTK3 in promoting integrin activity during breast cancer progression and metastasis.

Matched MeSH terms: Breast Neoplasms/pathology*
Gene expression analysis in MCF-7 breast cancer cells treated with recombinant bromelain

Fouz N, Amid A, Hashim YZ

Appl Biochem Biotechnol, 2014 Aug;173(7):1618-39.
PMID: 24928548 DOI: 10.1007/s12010-014-0947-6

The contributing molecular pathways underlying the pathogenesis of breast cancer need to be better characterized. The principle of our study was to better understand the genetic mechanism of oncogenesis for human breast cancer and to discover new possible tumor markers for use in clinical practice. We used complimentary DNA (cDNA) microarrays to compare gene expression profiles of treated Michigan Cancer Foundation-7 (MCF-7) with recombinant bromelain and untreated MCF-7. SpringGene analysis was carried out of differential expression followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We identified 1,102 known genes differentially expressed to a significant degree (p<0.001) changed between the treatment. Within this gene set, 20 genes were significantly changed between treated cells and the control cells with cutoff fold change of more than 1.5. These genes are RNA-binding motif, single-stranded interacting protein 1 (RBMS1), ribosomal protein L29 (RPL29), glutathione S-transferase mu 2 (GSTM2), C15orf32, Akt3, B cell translocation gene 1 (BTG1), C6orf62, C7orf60, kinesin-associated protein 3 (KIFAP3), FBXO11, AT-rich interactive domain 4A (ARID4A), COPS2, TBPL1|SLC2A12, TMEM59, SNORD46, glioma tumor suppressor candidate region gene 2 (GLTSCR2), and LRRFIP. Our observation on gene expression indicated that recombinant bromelain produces a unique signature affecting different pathways, specific for each congener. The microarray results give a molecular mechanistic insight and functional effects, following recombinant bromelain treatment. The extent of changes in genes is related to and involved significantly in gap junction signaling, amyloid processing, cell cycle regulation by BTG family proteins, and breast cancer regulation by stathmin1 that play major roles.

Matched MeSH terms: Breast Neoplasms/pathology*
Fulltext Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease

Peng HH, Huang KG, Chueh HY, Adlan AS, Chang SD, Lee CL

Taiwan J Obstet Gynecol, 2014 Sep;53(3):397-400.
PMID: 25286799 DOI: 10.1016/j.tjog.2013.02.005

OBJECTIVE: A twin pregnancy consisting of a complete hydatidiform mole with a coexisting normal fetus is extremely rare with an incidence of 1/22,000 to 1/100,000. The incidence of preterm delivery is high and few pregnancies reach near term with a viable fetus.
CASE REPORT: A 34-year-old woman presented at 20 weeks of gestation with increased levels of serum beta human chorionic gonadotropin (beta-HCG) at 4.74 multiples of the median (310277.7 mIU/mL). Ultrasonography showed a hydatidiform mole together with a normal fetus. Fetal karyotyping revealed 46XY. The serum beta-HCG levels were followed up throughout the remainder of the pregnancy. A male infant weighting 2260 g and the molar tissue were delivered at 37 weeks of gestation. The karyotype of the molar tissue showed 46XX and the histopathological report confirmed our diagnosis. At 4 months postpartum, metastatic gestational trophoblastic disease of the lung was diagnosed in the mother by a computed tomography scan due to increased beta-HCG levels. The patient received three unsuccessful cycles of methotrexate and folinate. Another four cycles of chemotherapy consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) were initiated and the beta-HCG levels returned to normal. There was no evidence of recurrence in the subsequent 5 years of regular follow up.
CONCLUSION: A pregnancy with a complete hydatidiform mole and a living cotwin can be a serious threat to the health of both the mother and the fetus. Early diagnosis depends on a combination of detecting an unusually high level of serum beta-HCG and ultrasound examination. We suggest that continuation of the pregnancy may be an acceptable option and that the pregnancy may continue until term if a normal fetal anatomy is assured and maternal complications are under control. Patients require careful postpartum follow up and any recurrent disease should be managed aggressively.
KEYWORDS: EMA-CO; metastatic gestational trophoblastic disease; twin pregnancy with one complete hydatidiform mole

Matched MeSH terms: Uterine Neoplasms/pathology*
Fulltext Descriptive epidemiology of colorectal cancer in University Malaya Medical Centre, 2001 to 2010

Magaji BA, Moy FM, Roslani AC, Law CW

Asian Pac J Cancer Prev, 2014;15(15):6059-64.
PMID: 25124558

BACKGROUND: Colorectal cancer is the second most frequent cancer in Malaysia. Nevertheless, there is little information on treatment and outcomes nationally. We aimed to determine the demographic, clinical and treatment characteristics of colorectal cancer patients treated at the University Malaya Medical Centre (UMMC) as part of a larger project on survival and quality of life outcomes.

MATERIALS AND METHODS: Medical records of 1,212 patients undergoing treatment in UMMC between January 2001 and December 2010 were reviewed. A retrospective-prospective cohort study design was used. Research tools included the National Cancer Patient Registration form. Statistical analysis included means, standard deviations (SD), proportions, chi square, t-test/ ANOVA. P-value significance was set at 0.05.

RESULTS: The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years. Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62 versus 62 years, p<0.001). More females (56%) had colon cancers compared to males (44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%) and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with Dukes' C and D accounting for 64%. Stage was not affected by age, gender, ethnicity or tumor site. Treatment modalities included surgery alone (40%), surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%).

CONCLUSIONS: Significant ethnic differences in age and site distribution, if verified in population-based settings, would support implementation of preventive measures targeting those with the greatest need, at the right age.

Matched MeSH terms: Colorectal Neoplasms/pathology

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