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1.
Int J Oral Maxillofac Surg ; 51(3): 289-299, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34154876

ABSTRACT

Circulating tumour cells (CTCs) are cancer cells released by cancer into the peripheral circulation. Haematogenous tumour spread is a hallmark of metastatic malignancy and a key factor in cancer recurrence and prognosis. CTCs have diagnostic and prognostic significance for a number of adenocarcinomas and melanoma. A review of the published peer-reviewed literature was performed to determine the clinical relevance of CTCs as a biomarker in the management of oral squamous cell carcinoma (OSCC). Fourteen studies met the eligibility criteria. With regard to patients with OSCC, this review found the following: (1) CTCs have been detected using multiple techniques; (2) the presence of CTCs does not appear to be related to tumour differentiation or size; (3) CTCs may be detected without lymph node involvement; (4) the detection of CTCs may be prognostic for both disease-free survival and overall survival; (5) quantification of CTCs may reflect the efficacy of therapy; (6) CTCs may be of value for ongoing patient monitoring. Preliminary evidence suggests that CTCs have diagnostic and prognostic potential as a biomarker for oral cancer management and warrant further investigation to determine their appropriate place in the management of OSCC patients.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Neoplastic Cells, Circulating , Biomarkers, Tumor , Carcinoma, Squamous Cell/pathology , Humans , Mouth Neoplasms/pathology , Neoplasm Recurrence, Local , Neoplastic Cells, Circulating/pathology , Prognosis , Squamous Cell Carcinoma of Head and Neck
2.
Crit Rev Oncol Hematol ; 90(3): 220-32, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24388103

ABSTRACT

BRAF is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Due to the commonality of BRAF mutations, a number of BRAF inhibitors have been developed as tools in the management of patients with cancers dependent on the action of mutant BRAF to drive cellular proliferation. In this review, we examine the current state of clinical trials and laboratory research concerning BRAF inhibitors in development and available for clinical use. We contrast the effectiveness of type-I and type-II BRAF inhibitors, the former typically showing much more restricted inhibitory selectivity and greater patient response rates.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Antineoplastic Agents/classification , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Molecular Targeted Therapy , Protein Kinase Inhibitors/classification
3.
Clin Transl Oncol ; 16(5): 425-35, 2014 May.
Article in English | MEDLINE | ID: mdl-24458880

ABSTRACT

Although there have been recent advances in the treatment of metastatic colorectal cancer, particularly with systemic chemotherapy, new biological agents and surgical metastasectomy, the disease remains difficult to treat. To personalise the management of mCRC and optimise patient outcomes, it is vital to acquire a deeper understanding of its natural history and mechanisms behind disease progression. This may be achieved by extensive study of tumour biomarkers: proteins or genetic alterations within neoplastic cells or their surrounding stroma that may be used to predict patient outcomes, disease trajectory and response to various therapies. The discovery of mutant Kirsten-RAS in determining patients who may be refractory to anti-epidermal growth factor receptor treatments has reinvigorated and reiterated the importance of our attempts to individualise cancer care. While many biomarkers have been studied and shown promise in the setting of mCRC, they are, with the exception of K-ras testing not used currently in a clinical setting due to conflicting results, small patient samples and methodological variations. Larger, multi-centric studies with uniform methods of tumour marker study are required to effectively tailor systemic therapies and select appropriate candidates for surgical metastasectomy.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms/pathology , Biomarkers, Tumor/genetics , Cell Cycle/genetics , Colorectal Neoplasms/genetics , Genes, Tumor Suppressor , Genomic Instability , Humans , Neoplasm Metastasis , Neovascularization, Pathologic , Oncogenes/genetics , Prognosis
4.
Exp Mol Pathol ; 95(3): 336-42, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24161954

ABSTRACT

B-Raf is one of the more commonly mutated proto-oncogenes implicated in the development of cancers. In this review, we consider the mechanisms and clinical impacts of B-Raf mutations in cancer and discuss the implications for the patient in melanoma, thyroid cancer and colorectal cancer, where B-Raf mutations are particularly common.


Subject(s)
Mutation/genetics , Neoplasms/genetics , Proto-Oncogene Proteins B-raf/genetics , Humans , Neoplasms/pathology
5.
Phys Chem Chem Phys ; 14(7): 2417-26, 2012 Feb 21.
Article in English | MEDLINE | ID: mdl-22249506

ABSTRACT

Aromatic radicals form in a variety of reacting gas-phase systems, where their molecular weight growth reactions with unsaturated hydrocarbons are of considerable importance. We have investigated the ion-molecule reaction of the aromatic distonic N-methyl-pyridinium-4-yl (NMP) radical cation with 2-butyne (CH(3)C≡CCH(3)) using ion trap mass spectrometry. Comparison is made to high-level ab initio energy surfaces for the reaction of NMP and for the neutral phenyl radical system. The NMP radical cation reacts rapidly with 2-butyne at ambient temperature, due to the apparent absence of any barrier. The activated vinyl radical adduct predominantly dissociates via loss of a H atom, with lesser amounts of CH(3) loss. High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry allows us to identify small quantities of the collisionally deactivated reaction adduct. Statistical reaction rate theory calculations (master equation/RRKM theory) on the NMP+2-butyne system support our experimental findings, and indicate a mechanism that predominantly involves an allylic resonance-stabilized radical formed via H atom shuttling between the aromatic ring and the C(4) side-chain, followed by cyclization and/or low-energy H atom ß-scission reactions. A similar mechanism is demonstrated for the neutral phenyl radical (Ph˙)+2-butyne reaction, forming products that include 3-methylindene. The collisionally deactivated reaction adduct is predicted to be quenched in the form of a resonance-stabilized methylphenylallyl radical. Experiments using a 2,5-dichloro substituted methyl-pyridiniumyl radical cation revealed that in this case CH(3) loss from the 2-butyne adduct is favoured over H atom loss, verifying the key role of ortho H atoms, and the shuttling mechanism, in the reactions of aromatic radicals with alkynes. As well as being useful phenyl radical analogues, pyridiniumyl radical cations may form in the ionosphere of Titan, where they could undergo rapid molecular weight growth reactions to yield polycyclic aromatic nitrogen hydrocarbons (PANHs).


Subject(s)
Alkynes/chemistry , Free Radicals/chemistry , Gases/chemistry , Pyridinium Compounds/chemistry , Cations/chemistry , Cyclization , Kinetics , Models, Theoretical
6.
Eur J Surg Oncol ; 37(1): 93-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21093207

ABSTRACT

BACKGROUND AND OBJECTIVES: Polymorphisms of the VEGF gene are known to affect the biological behaviour of cancers but have seldom been studied in thyroid cancer. The aim of the current study is to evaluate the prevalence and relevance of VEGF-A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Genomic DNA and total RNA were isolated from paraffin-embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and 78 control thyroid tissues. Three DNA polymorphisms (+936C > T, +405C > G and -141A > C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues was studied by real-time PCR. RESULTS: Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (p = 0.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (p = 0.009). Within the group of patients with conventional PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA expression than other patients (p = 0.0003). CONCLUSION: These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.


Subject(s)
Adenocarcinoma, Papillary/genetics , Biomarkers, Tumor/biosynthesis , Polymorphism, Single Nucleotide , Thyroid Neoplasms/genetics , Vascular Endothelial Growth Factor A/biosynthesis , Adenocarcinoma, Papillary/metabolism , Adult , Biomarkers, Tumor/genetics , Female , Humans , Male , Middle Aged , Phenotype , RNA, Messenger/biosynthesis , Thyroid Neoplasms/metabolism , Vascular Endothelial Growth Factor A/genetics
7.
Ann Surg Oncol ; 15(9): 2500-5, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18581185

ABSTRACT

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a notoriously aggressive malignancy associated with a highly lethal clinical course despite therapeutic intervention. Our present study attempts to identify factors that could potentially improve therapeutic strategies by analyzing the clinicopathological features, treatment and outcome of ATC patients managed over the past four decades at our institution. METHODS: Fifty patients with biopsy-proven ATC during the period 1966 to 2006 were studied. All patients were managed with surgery, radiotherapy, chemotherapy and/or chemoradiation. Survival was calculated by the Kaplan-Meier method. Potential factors affecting survival were compared by the log rank test. RESULTS: Most patients (88%) presented with a neck mass; 17 patients (34%) also had cervical lymphadenopathy. Distant metastases were clinically present in 9 (18%). Median survival was 97 days, whereas the 1- and 3-year survival was 14% and 8%, respectively. On univariate analysis, patients aged

Subject(s)
Carcinoma/mortality , Carcinoma/therapy , Thyroid Neoplasms/mortality , Thyroid Neoplasms/therapy , Thyroidectomy , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Carcinoma/radiotherapy , Carcinoma/surgery , Combined Modality Therapy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Survival Rate , Thyroid Neoplasms/pathology , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Treatment Outcome
8.
Postgrad Med J ; 84(988): 78-82, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18322127

ABSTRACT

The follicular variant of papillary thyroid carcinoma (FVPTC) presents a type of papillary thyroid cancer that has created continuous diagnosis and treatment controversies among clinicians and pathologists. In this review, we describe the nomenclature, the clinical features, diagnostic problems and the molecular biology of FVPTC. It is important for clinicians to understand this entity as the diagnosis and management of this group of patient may be different from other patients with conventional PTC. The literature suggests that FVPTC behaves in a way similar, clinically, to conventional papillary thyroid carcinoma. However, there are some genotypic differences which may characterise this neoplasm. These parameters may account for the phenotypic variation described by some scientists in this type of cancer. Further understanding can only be achieved by defining strict pathological criteria, in-depth study of the molecular biology and long term follow-up of the optional patients with FVPTC.


Subject(s)
Carcinoma, Papillary, Follicular/diagnosis , Thyroid Neoplasms/diagnosis , Carcinoma, Papillary, Follicular/genetics , Carcinoma, Papillary, Follicular/therapy , Diagnosis, Differential , Genes, ras/genetics , Humans , Mutation , PAX8 Transcription Factor , PPAR gamma/genetics , Paired Box Transcription Factors/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/therapy
9.
J Clin Pathol ; 59(1): 101-4, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16394289

ABSTRACT

AIMS: To determine the extent of Fas expression in oesophageal squamous cell carcinomas (ESCCs) from Chinese patients and to correlate Fas expression with clinicopathological prognostic parameters. METHODS: Clinicopathological data were collected from 58 patients with ESCC who underwent oesophagectomy and had no prior radiotherapy or chemotherapy. Immunostaining was performed on the primary tumours. Expression of Fas was correlated with patients' demographics, tumour characteristics and stage, R category of surgery, and patients' survival. RESULTS: The actuarial survival rates of all patients at two and five years after surgery were 48% and 14%, respectively. Fas expression was detected in 89.7% of ESCCs. Higher Fas expression recorded on a four point scale correlated with better tumour differentiation (p < 0.01), but not with other patient or tumour variables. Importantly, higher Fas expression was associated with better survival (p = 0.0317). CONCLUSIONS: These findings suggest that Fas activated apoptosis is important in the pathogenesis of ESCC. This molecular pathway may be a potential therapeutic target for ESCC.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , fas Receptor/metabolism , Adult , Aged , Apoptosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy , Female , Humans , Male , Middle Aged , Neoplasm Proteins/metabolism , Neoplasm Staging , Prognosis , Survival Analysis
10.
Eur J Cancer ; 39(13): 1881-7, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12932666

ABSTRACT

Epigenetic silencing of the p16 and p15 genes by promoter methylation are commonly observed in human epithelial malignancies, including head and neck squamous cell carcinomas (HNSCC). In this study, a methylation-specific polymerase chain reaction (MSP) was used to evaluate the methylation status of the p16 and p15 genes in 73 HNSCC surgical specimens. p16 and p15 gene methylation was also examined in 29 paired metastatic lymph nodes and 29 paired histologically, normal resection margin mucosae. The quantity of cell-free methylated p16 and p15 DNA in the plasma samples of 20 HNSCC patients and 24 healthy controls was also examined using a fluorescence-based real-time PCR assay. The frequencies of p16 and p15 methylation in the primary tumour were 49% and 60%, respectively. Concordant methylation of p16 and p15 in tumour samples and metastatic lymph nodes was found in 59 and 38% of cases, respectively. A significantly higher prevalence of p15 methylation was found in histologically-normal surgical margin epithelia of HNSCC patients with chronic smoking and drinking habits compared with non-smokers and non-drinkers. In addition, methylated p16 and p15 DNA levels were significantly higher in the plasma of HNSCC patients (mean 56 copies/ml plasma and 65 copies/ml plasma, respectively) compared with normal controls (mean 6 copies/ml plasma and 16 copies/ml plasma, respectively). In conclusion, promoter methylation of the p16 and p15 genes is involved in the pathogenesis of HNSCC and may be related to chronic smoking and drinking. The differential levels of methylated p16 and p15 DNA in plasma might be potential useful markers in screening high-risk populations for early HNSCC and monitoring their treatment response.


Subject(s)
Carcinoma, Squamous Cell/genetics , Cell Cycle Proteins , Genes, p16/physiology , Head and Neck Neoplasms/genetics , Transcription Factors/genetics , Tumor Suppressor Proteins , Adult , Aged , Aged, 80 and over , Cyclin-Dependent Kinase Inhibitor p15 , DNA Methylation , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction/methods
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