MyMedR

Dysregulation of microRNAs (miRNAs) has been implicated in almost every known survival mechanisms utilized by cancer cells. One of such mechanisms, anoikis resistance, plays a pivotal role in enabling metastasis by allowing cancer cells to circumvent cell death induced by lack of attachment. Understanding how miRNAs regulate the various anoikis pathways has become the research question of increasing number of studies published in the past years. Through these studies, a growing list of miRNAs has been identified to be important players in promoting either anoikis or resistance to anoikis. In this review, we will be focusing on these miRNAs and how the findings from those studies can contribute to novel therapeutic strategies against cancer progression. We will be examining miRNAs that have been found to promote anoikis sensitivity in numerous cancer types followed by miRNAs that inhibit anoikis. In addition, we will also be taking a look at major signaling pathways involved in the action of the each of these miRNAs to gain a better understanding on how miRNAs regulate anoikis.

Matched MeSH terms: Neoplasm Metastasis

Fulltext Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study

Miao H, Hartman M, Bhoo-Pathy N, Lee SC, Taib NA, Tan EY, et al.

PLoS One, 2014;9(4):e93755.

PMID: 24695692 DOI: 10.1371/journal.pone.0093755

BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia.
MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic).
RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66).
CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

Matched MeSH terms: Neoplasm Metastasis/pathology*

Metastatic tumours of the jaws

Chan YF

Med J Malaya, 1972 Sep;27(1):48-51.

PMID: 4264825

Matched MeSH terms: Neoplasm Metastasis*

Fulltext INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance

F Smit E, Dooms C, Raskin J, Nadal E, Tho LM, Le X, et al.

Future Oncol, 2022 Mar;18(9):1039-1054.

PMID: 34918545 DOI: 10.2217/fon-2021-1406

MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-a-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov).

Matched MeSH terms: Neoplasm Metastasis*

Fulltext Subcutaneous metastasis of olfactory neuroblastoma - an uncommon presentation

Chew YK, Cheong JP, Brito-Mutunayagam S, Khir A, Prepageran N, Mun KS

Med J Malaysia, 2011 Mar;66(1):62-3.

PMID: 23765147

Olfactory neuroblastoma is a rare, slow growing, malignant tumour of neuroectodermal origin that begins in neuroepithelial cells of the olfactory membrane. A metastatic rate of 20% to 60% is reported with the most common site being the cervical lymph node. Other sites include the parotid glands, skin, lungs, bone, liver, orbit, spinal cord and spinal canal. We describe a case of olfactory neuroblastoma presented to us with scalp metastasis.

Matched MeSH terms: Neoplasm Metastasis

Fulltext Leukaemic stem cells: drug resistance, metastasis and therapeutic implications

Wong RS, Cheong SK

Malays J Pathol, 2012 Dec;34(2):77-88.

PMID: 23424769 MyJurnal

Although there have been many new developments in the treatment of leukaemia with the use of new anti-leukaemic agents and stem cell transplantation, drug resistance and treatment failure remain a great challenge for the attending physician. Several studies have suggested that leukaemic stem cells (LSCs) play a pivotal role in chemoresistance and metastasis and the mechanisms by which these cells do so have also been elucidated. There is increasing evidence to show that there exists a large pool of therapeutic targets in LSCs and that the eradication of these cells is feasible with some promising results. This article gives an overview of different types of cancer stem cells (CSCs) derived from various types of leukaemia, the mechanisms by which LSCs contribute to drug resistance and metastasis and some recent advances in targeted therapy against LSCs.

Matched MeSH terms: Neoplasm Metastasis/immunology; Neoplasm Metastasis/pathology; Neoplasm Metastasis/therapy

Fulltext The Role of PPARβ/δ in Melanoma Metastasis

Lim JCW, Kwan YP, Tan MS, Teo MHY, Chiba S, Wahli W, et al.

Int J Mol Sci, 2018 Sep 20;19(10).

PMID: 30241392 DOI: 10.3390/ijms19102860

BACKGROUND: Peroxisome proliferator⁻activated receptor (PPAR) β/δ, a ligand-activated transcription factor, is involved in diverse biological processes including cell proliferation, cell differentiation, inflammation and energy homeostasis. Besides its well-established roles in metabolic disorders, PPARβ/δ has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPARβ/δ's role in tumour progression and metastasis remains controversial.

METHODS: In the present studies, the consequence of PPARβ/δ inhibition either by global genetic deletion or by a specific PPARβ/δ antagonist, 10h, on malignant transformation of melanoma cells and melanoma metastasis was examined using both in vitro and in vivo models.

RESULTS: Our study showed that 10h promotes epithelial-mesenchymal transition (EMT), migration, adhesion, invasion and trans-endothelial migration of mouse melanoma B16/F10 cells. We further demonstrated an increased tumour cell extravasation in the lungs of wild-type mice subjected to 10h treatment and in Pparβ/δ-/- mice in an experimental mouse model of blood-borne pulmonary metastasis by tail vein injection. This observation was further supported by an increased tumour burden in the lungs of Pparβ/δ-/- mice as demonstrated in the same animal model.

CONCLUSION: These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.

Matched MeSH terms: Neoplasm Metastasis/genetics*; Neoplasm Metastasis/pathology

Fulltext Solitary adrenal metastasis from invasive infiltrating ductal carcinoma: A case report and review of literature

Sangeetha Poovaneswaran, Justin Zon Ern Lee, Whei Ying Lim, Navarasi S Raja Gopal, Fauziah Mohd Dali, Ibtisam Mohamad

International e-Journal of Science, Medicine & Education, 2013;7(1):33-36.

MyJurnal

Solitary adrenal metastasis is a rare presentation in breast cancer and it presents the clinician with a difficult therapeutic dilemma as there are no existing guidelines for optimal management. On literature review, we only found one published case report of solitary adrenal metastasis from infiltrating ductal carcinoma of the breast. Here we present a case of a 75 year-old lady who presented with a right breast lump which was subsequently confirmed to be infiltrating ductal carcinoma. She underwent a right mastectomy and axillary clearance. Computerised tomography (CT) staging revealed a solitary adrenal metastasis. She was treated with aromatase inhibitors and her tumour markers which were initially raised has now normalised.

Matched MeSH terms: Neoplasm Metastasis

Primary sarcoma of the spleen

Singh P

Journal of the Malaya Branch of the British Medical Association, 1940;4:322-24.

A case of primary endothelial sarcoma of the spleen treated by splenectomy is described.

Matched MeSH terms: Neoplasm Metastasis

Fulltext The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

Ochieng J, Nangami GN, Ogunkua O, Miousse IR, Koturbash I, Odero-Marah V, et al.

Carcinogenesis, 2015 Jun;36 Suppl 1:S128-59.

PMID: 26106135 DOI: 10.1093/carcin/bgv034

The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis.

Matched MeSH terms: Neoplasm Metastasis/pathology*

Squamous cell carcinoma cervix stage IIIB metastatic to oral cavity: A case report and literature review

Purbadi S, Saspriyana KY, Rustamadji P

Med J Malaysia, 2020 07;75(4):450-451.

PMID: 32724016

Metastatic cervical cancers to the oral cavity are uncommon. These metastases most commonly present as lesions of the jaw bones and the mandible. A 57-year-old female patient complained of mass lesion in her oral cavity after definitive treatment for squamous cell carcinoma of the cervix stage IIIB. On examination a swelling of 3cm in size was found on the left side of buccal vestibule adjacent to the lower canine tooth. Wide local excision was performed, and histopathology results showed a squamous cell carcinoma of moderate differentiation. She was continued with segmental mandibulectomy, supraomohyoid neck dissection and plate-screw reconstruction. Radiotherapy was given as an adjuvant therapy.

Matched MeSH terms: Neoplasm Metastasis*

Histopathological study of carcinoma showing thymus-like differentiation (CASTLE)

Okubo Y, Sakai M, Yamazaki H, Sugawara Y, Samejima J, Yoshioka E, et al.

Malays J Pathol, 2020 08;42(2):259-265.

PMID: 32860379

INTRODUCTION: Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumour that mainly arises from the thyroid gland, or occasionally, from the head and neck. Although the 10-year survival rate of patients with CASTLE is approximately 80%, local recurrence and distant metastasis are observed in some cases. A recent systematic review for CASTLE indicated that the prognostic factors are treatment-dependent, and postoperative radiotherapy significantly improves patient survival.

CASE REPORT: Herein, we describe and compare three cases of CASTLE, including a case with distant metastasis despite administering postoperative chemotherapy. Thus, the mechanisms underlying metastasis of CASTLE are unclear. This case study helps to elucidate the histopathological risk factors of metastasis in CASTLE.

DISCUSSION: We found that prominent lymphovascular invasion and higher proliferative activities might be risk factors of metastasis in CASTLE. In addition, we have summarised the cytological, morphological, and immunohistochemical features of CASTLE for an accurate diagnosis.

Matched MeSH terms: Neoplasm Metastasis/pathology

ENDOMETRIAL CARCINOMA

MEARSES SD

Med J Malaysia, 1963 Jun;17:253-62.

PMID: 14065443

Matched MeSH terms: Neoplasm Metastasis*

The Role of MicroRNAs in Diagnosis, Prognosis, Metastasis and Resistant Cases in Breast Cancer

Teoh SL, Das S

Curr Pharm Des, 2017;23(12):1845-1859.

PMID: 28231756 DOI: 10.2174/1381612822666161027120043

The incidence and mortality due to breast cancer is increasing worldwide. There is a constant quest to know the underlying molecular biology of breast cancer in order to arrive at diagnosis and plan better treatment options. MicroRNAs (miRNAs) are small non-coding and single stranded RNAs which influence the gene expression and physiological condition in any tumor. The miRNAs may act on different pathways in various cancers. Recently, there are research reports on various miRNAs being linked to breast cancers. The important miRNAs associated with breast cancers include miR-21, miR-155, miR-27a, miR-205, miR-145 and miR-320a. In the present review we discuss the role of miRNAs in breast cancer, its importance as diagnostic markers, prognosis and metastasis markers. We also highlight the role of miRNAs with regard to resistance to few anticancerous drugs such as Tamoxifen and Trastuzumab. The role of miRNA in resistance to treatment is one of the core issues discussed in the present review. Much information on the miRNA roles is available particularly in the neoadjuvant chemotherapy setting, because this protocol allows the rapid association of miRNA expression with the treatment response. This review opens the door for designing better therapeutic options in drug resistance cases in breast cancer.

Matched MeSH terms: Neoplasm Metastasis/genetics*

Fulltext Characterization and potential roles of bone marrow-derived stromal cells in cancer development and metastasis

Kawai H, Tsujigiwa H, Siar CH, Nakano K, Takabatake K, Fujii M, et al.

Int J Med Sci, 2018;15(12):1406-1414.

PMID: 30275769 DOI: 10.7150/ijms.24370

Background: The tumor microenvironment and its stromal cells play an important role in cancer development and metastasis. Bone marrow-derived cells (BMDCs), a rich source of hematopoietic and mesenchymal stem cells, putatively contribute to this tumoral stroma. However their characteristics and roles within the tumor microenvironment are unclear. In the present study, BMDCs in the tumor microenvironment were traced using the green fluorescent protein (GFP) bone marrow transplantation model. Methods: C57BL/6 mice were irradiated and rescued by bone marrow transplantation from GFP-transgenic mice. Lewis lung cancer cells were inoculated into the mice to generate subcutaneous allograft tumors or lung metastases. Confocal microscopy, immunohistochemistry for GFP, α-SMA, CD11b, CD31, CD34 and CD105, and double-fluorescent immunohistochemistry for GFP-CD11b, GFP-CD105 and GFP-CD31 were performed. Results: Round and dendritic-shaped GFP-positive mononuclear cells constituted a significant stromal subpopulation in primary tumor peripheral area (PA) and metastatic tumor area (MA) microenvironment, thus implicating an invasive and metastatic role for these cells. CD11b co-expression in GFP-positive cells suggests that round/dendritic cell subpopulations are possibly BM-derived macrophages. Identification of GFP-positive mononuclear infiltrates co-expressing CD31 suggests that these cells might be BM-derived angioblasts, whereas their non-reactivity for CD34, CD105 and α-SMA implies an altered vascular phenotype distinct from endothelial cells. Significant upregulation of GFP-positive, CD31-positive and GFP/CD31 double-positive cell densities positively correlated with PA and MA (P<0.05). Conclusion: Taken together, in vivo evidence of traceable GFP-positive BMDCs in primary and metastatic tumor microenvironment suggests that recruited BMDCs might partake in cancer invasion and metastasis, possess multilineage potency and promote angiogenesis.

Matched MeSH terms: Neoplasm Metastasis*

Fulltext Differential expression of galectin-3 in advancing thyroid cancer cells: a clue toward understanding tumour progression and metastasis

Htwe TT, Karim N, Wong J, Jahanfar S, Mansur MA

Singapore Med J, 2010 Nov;51(11):856-9.

PMID: 21140111

INTRODUCTION: Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important role in cell-to-cell adhesion and in cell-to-matrix interaction. Cellular expression of galectin-3 is correlated with cancer aggressiveness and metastasis.
METHODS: We examined the differential expression of galectin-3 in a collection of 142 cases of thyroid lesions, including 108 cases of papillary thyroid carcinoma (PTC) and 34 cases of follicular carcinoma (FCA). An immunohistochemical method was applied and semiquantitative scoring was performed on the staining intensity of the positive tissue. Scoring was done on cells at the central portion of the tumour foci and on cells at the periphery that were adjacent to the neighbouring normal thyroid tissue matrix.
RESULTS: A significantly higher expression (p is 0.001) of galectin-3 was observed in the advancing peripheral thyroid cancer cells compared to the centrally located cells that were not in close contact with the neighbouring stromal tissue in cases with PTC compared to those with FCA.
CONCLUSION: This finding supported the role of galectin-3 in its cell-to-cell adhesion and cell-to-matrix interaction. Galectin-3 is a potential tumour marker for indicating local and distance metastasis, especially in cases with PTC.

Matched MeSH terms: Neoplasm Metastasis/pathology*

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