MyMedR

The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications

Teoh SL, Das S

Curr Drug Targets, 2017 Nov 30;18(16):1880-1892.

PMID: 27628948 DOI: 10.2174/1389450117666160907153338

BACKGROUND: The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression. The Hippo pathway (also known as the Salvador-Warts-Hippo pathway) is the latest emerging concept in cancers. The Hippo pathway plays an important role in controlling the size of the tissue and organ by virtue of its action on cell proliferation and apoptosis.

OBJECTIVE: In the present review, we highlight the mammalian Hippo pathway, role of its core members, its upstream regulators, downstream effectors and the resistance cases in lung cancers.

RESULTS: Specific interaction of Mer with cell surface hyaluronan receptor CD44 is vital in cell contact inhibition, thereby activating Hippo pathway. Both transcription co-activators YAP and TAZ (also known as WWTR1, being homologs of Drosophila Yki) are important regulators of proliferation and apoptosis, and serve as major downstream effectors of the Hippo pathway. Mutation of NF2, the upstream regulator of Hippo pathway is linked to the cancers.

CONCLUSION: Targeting YAP and TAZ may be important for future drug delivery and treatment.

Fulltext Personal Protective Equipment (PPE) and Its Use in COVID-19: Important Facts

Das S, Rajalingham S

Indian J Surg, 2020 May 28.

PMID: 32837060 DOI: 10.1007/s12262-020-02411-8

Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment

Teoh SL, Das S

Tumour Biol., 2016 Nov;37(11):14363-14380.

PMID: 27623943

Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

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.

Notch Signalling Pathways and Their Importance in the Treatment of Cancers

Teoh SL, Das S

Curr Drug Targets, 2018;19(2):128-143.

PMID: 28294046 DOI: 10.2174/1389450118666170309143419

BACKGROUND: The Notch pathway is an evolutionarily conserved, intercellular signalling system which is present in all multicellular organisms and mammals. The Notch pathway plays an important role in the embryonic development as it controls cell proliferation, cell differentiation and binary cell fate decisions.

OBJECTIVE: In the present review, we highlight the Notch signalling pathway components i.e. Notch receptors, ligands, effector, and their regulators. We also discuss the tumor biology of the Notch pathway involved in various cancers.

RESULTS: Interestingly, the Notch signalling pathway is dysregulated in many cancers. Notch may serve as oncogene or tumor suppressor and plays an important role in cancers of the liver, pancreas, endometrium of uterus, ovary, prostate, bladder and colon. The activation of Notch pathway plays a vital role in the progression of some cancer. In addition, Notch pathway activation was also shown to drive chemoresistance in cancer, as well. Chemotherapeutically, combined NOTCH1 inhibitor synergistically attenuated chemotherapy-enriched cancer stem cell population both in vitro and in vivo. This may prove to be beneficial in the treatment of cancer.

CONCLUSION: The Notch inhibitors possess anti-proliferative effects on cancer, thereby serving as a new treatment for cancer.

Dynamics of Diabetes and Obesity: An Alarming Situation in the Developing Countries in Asia

Chakraborty C, Das S

Mini Rev Med Chem, 2016;16(15):1258-1268.

PMID: 27145852 DOI: 10.2174/1389557516666160505115512

The incidence of diabetes in developing countries in Asia has increased over the last few years. The economic development is radically changing the lifestyle of the younger generation who prefer to embrace the western lifestyle of eating high calorie fast food with minimal physical exercise. Previously, the rate of diabetes was very low but it is increasing at an alarming rate in the developing countries in Asia. Admittedly, there is paucity of literature on the prevalence of patients with type-1 diabetes in Asian developing countries due to lower field surveys and lack of quantitative data. Few contributing factors such as body mass index (BMI) and its relation with obesity and diabetes, energy dense diet, excessive caloric intake, sedentary behaviors, lifestyle and family history, gene and genomewide association of diabetes, genes and gene polymorphisms are being discussed especially with regard to the Asian population. Dynamics of the diabetes and obesity was depicted for the population of Asian developing countries with special emphasis on China and India. Diabetes has become widespread among the low-income communities. Hence, it is necessary to develop appropriate healthcare policies in order to mitigate this rampant epidemic before it is too late.

The effect of alcohol level on male and female drivers: Important facts

Murthy JK, Das S

Drug Alcohol Depend, 2020 Sep 01;214:108146.

PMID: 32634715 DOI: 10.1016/j.drugalcdep.2020.108146

Fulltext Interesting facts regarding the marginal mandibular branch of the facial nerve

Hussan F, Das S

Indian J Plast Surg, 2010 Jul;43(2):231.

PMID: 21217995 DOI: 10.4103/0970-0358.73477

Fulltext Predictors of diastolic dysfunction in rheumatoid arthritis

Sakthiswary R, Das S

Saudi Med J, 2015 May;36(5):525-9.

PMID: 25935171 DOI: 10.15537/smj.2015.5.10751

The main objective was to determine the predictors of diastolic dysfunction in rheumatoid arthritis (RA). Articles pertaining to diastolic dysfunction in RA were retrieved from Scopus, EBSCO, PubMed, Web of Science, and Cochrane Library databases. Keywords such as: diastolic, cardiac, left ventricular function, heart failure, rheumatoid arthritis, and cardiac failure were used. Studies, which examined factors, or predictors of diastolic dysfunction in RA, and those with echocardiographic evaluation of diastolic dysfunction, were included. A total of 8 studies met the eligibility criteria. Most studies (6 out of 7 studies) demonstrated a significant inverse relationship between the E (early)/A (late) ratio and disease duration. The pooled analysis using the random effects model revealed a significant but weak inverse relationship between the ratio of the E to A ventricular filling velocities (E/A) ratio and the disease duration (p less than 0.05, r=-0.385). There was a significant relationship between E/A ratio and disease duration in RA.

Study site: Hospital Kuala Lumpur (HKL)

Fulltext Cardiorespiratory parameters before and after acupuncture: observations in a healthy and diseased state

Mohan V, Das S

Clinics (Sao Paulo), 2012;67(6):673-4.

PMID: 22760909

Comment on: Nascimento RC, Hossri CA, Berwanger O, Carvalho VO. Acupuncture and exercise capacity: a case report. Clinics. 2012;67(2):193–4

Gunshot wound in skeletonised human remains with partial adipocere formation

Mohd Nor F, Das S

J Forensic Leg Med, 2012 Jan;19(1):42-5.

PMID: 22152448 DOI: 10.1016/j.jflm.2011.07.008

We present a case of skeletonised human remains. In the present case report, a body was exhumed from the ground above a cemetery. On exhumation, the body was partially-skeletonised with adipocere formation on the upper part of the body. Autopsy of the body showed two bullets in the right thigh muscle and lumbar vertebrae between L4 and L5. Postmortem changes and destruction of soft tissue made it impossible to determine direction of fire through the body, even in a careful complete autopsy.

Fulltext Blood-brain barrier dysfunction in ischemic stroke and diabetes: the underlying link, mechanisms and future possible therapeutic targets

Wicha P, Das S, Mahakkanukrauh P

Anat Cell Biol, 2021 Jun 30;54(2):165-177.

PMID: 33658432 DOI: 10.5115/acb.20.290

Ischemic stroke caused by occlusion of cerebral artery is responsible for the majority of stroke that increases the morbidity and mortality worldwide. Diabetes mellitus (DM) is a crucial risk factor for ischemic stroke. Prolonged DM causes various microvascular and macrovascular changes, and blood-brain barrier (BBB) permeability that facilitates inflammatory response following stroke. In the acute phase following stroke, BBB disruption has been considered the initial step that induces neurological deficit and functional disabilities. Stroke outcomes are significantly worse among DM. In this article, we review stroke with diabetes-induce BBB damage, as well as underlying mechanism and possible therapeutic targets for stroke with diabetes.

Fulltext Placental histopathological changes in COVID-19 in term patients admitted to labor and delivery

Ahmad MFB, Das S

Am J Obstet Gynecol, 2021 09;225(3):353-354.

PMID: 34062121 DOI: 10.1016/j.ajog.2021.05.040

Fulltext Morphology of the human aorta and age-related changes: anatomical facts

Komutrattananont P, Mahakkanukrauh P, Das S

Anat Cell Biol, 2019 Jun;52(2):109-114.

PMID: 31338225 DOI: 10.5115/acb.2019.52.2.109

Aorta is the largest artery in the human body. Its starting point is the aortic orifice of the aortic valve and it terminates at the level of the fourth lumbar vertebra. The main function of the aorta is to transport oxygenated blood to supply all the organs and cells. With advancing age, the structure and hence the function show progressive changes. Various changes in the aortic morphology include the luminal diameter of aorta, whole length of the aorta, thickness, the microstructural components also change, and these include collagen, elastin and smooth muscle cells. In addition, the dimensions of all segments of the aorta increase with age in both sexes. Since age is a major risk factor for degenerative change and diseases affecting the aorta, understanding the detailed anatomy of the aorta may provide essential information concerning the age-associated process of the aorta. Knowledge of the morphological changes in the aorta is also important for future clinical therapies pertaining to aortic disease. Additionally, the information regarding the structural changes with age may be applied for age determination. This review describes the overview of the anatomy of the aorta, age related changes in the morphology of the aorta and aortic diseases.

Fulltext Vienna nomogram-based prostate biopsy: can it be a much better diagnostic tool than other conventional prostate biopsies?

Ho CC, Ho SE, Das S

Korean J Urol, 2014 Sep;55(9):628.

PMID: 25237467 DOI: 10.4111/kju.2014.55.9.628

Re: Giorgio Gandaglia, Alberto Briganti, Graham Jackson, et Al. A systematic review of the association between erectile dysfunction and cardiovascular disease. Eur urol 2014;65:968-78

Ho CC, Ho SE, Das S

Eur Urol, 2014 Nov;66(5):e87.

PMID: 24951360 DOI: 10.1016/j.eururo.2014.06.003

Clinical importance of duplicated internal jugular vein

Das S, Ho CK, Eng HS

Br J Oral Maxillofac Surg, 2014 Oct;52(8):773.

PMID: 24947333 DOI: 10.1016/j.bjoms.2014.05.015