Molecular Biomarkers & Diagnosis

Metastasis among the cancer patients results in poor prognosis and reduces overall survival drastically. Biomarkers of cancer are present in various body fluids and tissues which may be detected easily. Discovery of these biomarkers has led to tremendous improvement in diagnosis and clinical outcome of cancer patients. Circulating tumor cells (CTCs) are one such bio fluid based markers which have been extensively studied in current times as diagnostic, predictive and prognostic markers.

Background: Early diagnosis of transient tachypnea of newborn (TTN) is important for early treatment and good prognosis, but it is misdiagnosed with some diseases t hat occur in neonates like neonatal sepsis.

Aim: The study aims at investigating lactate, lactate dehydrogenase(LDH) and cystatin-C (Cys-C) as markers for early diagnosis of TTN.

Patients and methods: Blood samples taken within 1 hour after birth from 40 neonates who later developed TTN and from 40 neonates who did not develop TTN as a control group. Eighty neonates who were admitted to the NICU at Tanta University Hospital with gestational age above 37 weeks during the period 12 months (from December 2011 to May 2012, were included in this study. Neonates with RD during the first 24 hours of life constituted the patient group (n=40; 28 male: 12 female) and neonates without respiratory problems constituted the control group (n=40; 20 male; 20 female), written informed consent was obtained from all parents.

Results: Babies with TTN showed significantly higher levels of lactate, lactate dehydrogenase activity (LDH) and cystatin-C (Cys-C) level (P<0.05) in their serum than babies without TTN who act as a control group.When using the value of 2.2 pg/ml for serum lactate as a cutoff value the sensitivity was 92%, the specificity was 85%, the +PV% was 87% and the -PV% was 81% and the accuracy was 88. When using the value of 920 IU/L for serum LDH as a cutoff value the sensitivity was 94%, the specificity was 87%, the +PV% was 89% and the -PV% was 82% and the accuracy was 90. When using the value of 1.73 mg/ L for Cyst-C as a cutoff value the sensitivity was 96%, the specificity was 90%, the +PV% was 94% and the -PV% was 87% and the accuracy was 92%.

Conclusion: Serum lactate level, LDH activity and Cys-C level increased in babies with TTN if compared with babies without TTN. Hence lactate,LDH and Cys-C can be used for early diagnosis of TTN and early treatment with better prognosis.

This mini-review presents the current state of our knowledge of biomarkers in the selected oncology research area of “adipose tumors”: lipomas (benign) and liposarcomas. (malign). To our awareness never before have clear arguments been given underpinning a hypothesis that convincingly stated that malignant transformation from a lipoma can occur towards a liposacroma based on a biochemical model. Acidic pH-due to lactic acid- derived from cancer cells may induce failed reprogramming of normal differentiated cells adjacent tumor cells and turn them into cancer cells. An important observation at this cellular response of aerobic fermentation (“Warburg effect”) is that it occurs already at pre-carcinogenic conditions so it has another major aiming, we hypothesize to maintain the redox balance in combination with glutaminolysis and reversed β-oxidation in order to keep the Krebs cycle spinning. This peculiar observation convinced us-after studying obesity and two novel biomarkers for type 2 diabetes-that most cancers are a metabolic and redox balance disease. In addition, we describe the present role of Lipoproteins like cholesterol as carrier of anti-cancer medicine but hypothesize simultaneously that “fat particles” carried by lipoproteins can result in metastasis of “lipid tumors”. We give four demands for a suitable biomarker-not only for a metabolomics based on a lipidomics based approach-but in general. The final culprit of this review is the biochemical model for this 36:1 phosphatidylcholine biomarker which was not only found in all non-adipose tissue but also in the blood. Hypoxic conditions in white adipose tissue (WAT) either during obesity, either in the microenvironment of an adipose tumor will result in further growth based of fatty acid (FA) chain elongation based on a reversal of the β-oxidation under hypoxia in order to maintain the redox balance and keep the Krebs cycle spinning.

Background: Cataractous lenses represent one of the main public health problem involved in impairing vision. Different multiactorial agents are involved in its development.

Material and methods: In this study, 15 congenital and 56 senile cataractous lenses obtained post-operative surgery from patients admitted to Ophthalmic Center, Mansoura University Hospital, Mansoura, Egypt were investigated. Non-opaque lenses were extracted from infants aging 8 M-2 y-old (n=5) and young adult 20-30 years (n=6) after accident death of 1-4 hours. Medical Research Ethics committee, Egypt, approved the study protocol. A written informed consent had been taken beforehand from all patients or parent of infants to use their extracted lens experimentally after operation. Biochemical analysis was carried out to outline the differences between congenital and senile cataractous lenses in comparison with the control. Different parameters were investigated including amino acids, protein carbonylation, glycation end products, phospholipids, caspases, endothelin, heat shock protein, sorbitol, fructose and comet assay for single DNA damaged and scanning electron microscopy of lens fibres were investigated.

Results: The findings revealed marked increase of protein carbonylation, glycation end products, phospholipids, caspases, endothelin, heat shock protein, sorbitol and fructose coincides with single DNA damage. Aspartic, alanine, cysteine, isoleucine, leucine, methionine, tyrosine, histidine, tryptophan, valine and phenylalanine were significantly decreased in senile cataractous lenses in comparison with control and congenital cataracts. Scanning electron microscopy revealed abnormal disorganized lens fibers in cataractous lens which become widely separated and possessed deformation of ball and sockets. Some lens fibers possessed apparent accumulation of calcium salts.

Conclusions: Different factors are involved in cataractous formation coincides with increased of glycation end products and caspases reflecting apoptosis of lens.

The prevalence of patients with chronic pain who display depressive symptoms is quite high, with depression potentially an integral component of chronic pain. Since the current subjective clinical diagnostic systems were not designed to assess depression in patients with chronic pain, they fail to adequately capture the nature of mood states of these patients. It is difficult to apply these assessment tools to segregate unipolar depression (MDD) from the demoralization inherent in chronic pain states. MDDScore™, a multivariate biomarker blood test for depression, was used to determine if it was possible to identify biomarker patterns consistent with major depressive disorder in multiple chronic pain states. Three study groups were analyzed, and included: (i) patients (n=93) with centralized Chronic Intractable Pain (CIP), (ii) patients (n=20) with chronic pain of diverse origin from Scripps Pain Clinic (SPC) and (iii) prospectively collected patients (n=28) with comorbid arthritis and depressive symptoms. A very distinct bimodal pattern was observed. Forty-nine of 93 CIP patients (52.7%), 18 of 28 (64.2%) of the arthritis patients, and 9 of 20 (45%) patients with chronic pain of diverse origin from Scripps Pain Clinic had MDDScores of ≥5. Thus, the biomarker panel could segregate patients into two major groups based upon MDDScores. These data suggest but not prove we can objectively identify chronic pain patients with a higher probability of comorbid major depression.

Importantly, we can use the biomarkers on the MDDScore panel to gain insight into and gauge the residual (post-treatment) level of inflammation in these intensively treated patients. To this end, we determined and compared the serum concentrations of alpha-1 antitrypsin (A1AT), Myeloperoxidase (MPO) and soluble tumor necrosis factor receptor type 2 (sTNFR2) in each of the patient populations studied.

A female with suspected Down syndrome was born by vaginal delivery at 37 weeks 2 days’ gestation to a mother with a history of Type A2 gestational diabetes mellitus. Routine prenatal testing consisted of a non-invasive screening test for aneuploidy. Results, presented in Table 1, indicated an aneuploidy for trisomy of chromosome 21, indicating an increased risk for Down syndrome.

The animate needs water to survive and human being is not an exception; however, it could be fatal in some circumstances. Quantity and quality of the consumed water as well as time, place, habit, health status, and individual characteristics contribute to daily water need. According to Avicenna's viewpoint, drinking too much water and/ or drinking water without thirst is harmful for the body. Avicenna cited that the person who drink too cold water would see the side effects of this unhealthy habit sooner or later, although may not feel any discomfort or illness at the time. ''Drink to thirst'' is considered a consensus versus to ''drink to max'' in order to prevent exercise-induced hyponatremia.

Once again natural management of symptomatic and lifestyle dependant illness can be seen as a bit of an industry pioneer in terms of results. In my field of fertility related illness and disease the correctly implemented and managed system of drug free intervention has quite unnatural results. Let’s take a look specifically at PCOS an area in which i have long established and accountable, proven results. PCOS is a condition linked to poor fertility, but it does have other implications that are likely to affect a woman on a day to day basis.

This study reports on the development of a novel serum protein panel of three prostate cancer biomarkers, Filamin A, Filamin B and Keratin-19 (FLNA, FLNB and KRT19) using multivariate models for disease screening and prognosis. ELISA and IPMRM (LC-MS/MS) based assays were developed and analytically validated by quantitative measurements of the biomarkers in serum. Retrospectively collected and clinically annotated serum samples with PSA values and Gleason scores were analyzed from subjects who underwent prostate biopsy, and showed no evidence of cancer with or without indication of prostatic hyperplasia, or had a definitive pathology diagnosis of prostatic adenocarcinoma. Probit linear regression models were used to combine the analytes into score functions to address the following clinical questions: does the biomarker test augment PSA for population screening? Can aggressive disease be differentiated from lower risk disease, and can the panel discriminate between prostate cancer and benign prostate hyperplasia? Modelling of the data showed that the new prostate biomarkers and PSA in combination were better than PSA alone in identifying prostate cancer, improved the prediction of high and low risk disease, and improved prediction of cancer versus benign prostate hyperplasia.

According to a generally accepted theory development of a tumor is the results of an arrest or blockage in the differential pathway of a given cell. Most neoplasms have a reasonably constant, exponential growth rate throughout the majority of their life span. This is an important biological feature in neoplasia because it predicts the length of time required for a single neoplastic cell to reach a mass of 1 cm in diameter. This is approximately 30 population doublings and is three times longer than the length of time required to grow from 1 cm to a near lethal 1 kg mass (which requires only an additional 10 population doublings). Thus, about 75% of the life span of (untreated) neoplasms occurs prior to development of symptoms, since small tumors are generally clinically silent. It is especially sobering to note that, on average, carcinomas require a metastatic phenotype (or characteristics) between the 8th and 12th population doubling.

27-year-old female patient with history of migraine with sensory aura. Approximately four months previous to her admission, her migraines were increasing in frequency; due to this, she increased her dose of sumatriptan. One month previous to her admission, she presented an acute episode of the “worst migraine attack in her life”, without any associated focal neurology. Despite reducing in intensity, the headache persisted from that day onwards. After approximately one week, she developed neurobehavioral changes, which progressively worsened. Her CT on admission showed a hypo density in the right anterior thalamus; an MRI done three days later demonstrated a chronic (>3 weeks old) right thalamic stroke. The “worst migraine of her life” correlates well with the occurrence of the right thalamic stroke. The previously increased dose of sumatriptan seems to have precipitated the event and, the neurobehavioral changes fit nicely with the anterior damage to the thalamus.