A Poor Prognostic ALK Phenotype: A Review of Molecular Markers of Poor Prognosis in ALK Rearranged Nonsmall Cell Lung Cancer.

Background: Patients with nonsmall cell lung cancer with anaplastic lymphoma kinase (ALK) rearrangements derive a significant and durable clinical benefit from tyrosine kinase inhibitors (TKIs). However, early progression/death on treatment occurs in a subset of patients, which we term the poor prognostic ALK phenotype. This review aims to summarize the known molecular mechanisms that underlie this phenotype with a focus on variant 3 and TP53 mutations.

Adaptive Universal Principles for Real-world Observational Studies (AUPROS): an approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research.

The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342).

Treatment patterns and outcomes in KRAS-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study.

Objectives: KRAS mutations, particularly KRAS, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRAS-positive advanced NSCLC receiving systemic therapy post-ICI treatment.

Golgi fragmentation - One of the earliest organelle phenotypes in Alzheimer's disease neurons.

Alzheimer's disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model.

Tree nuts supplementation instigates the oxidative status and improves brain performance in male rats.

Exposure to cadmium has been extensively increased due to its usage in modern daily life. Inside the human body it induces deteriorating effects in every vital organ including brain. Oxidative stress has been widely implicated in neurotoxicity induced by cadmium exposure.

Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts.

Cadmium, a heavy metal with no physiological function in the human body, is considered a bio-hazard. It is also considered to be a potent neurotoxin. The primary sources of cadmium exposure are diet and cigarette smoke.

Pulmonary arterial hypertension: A rare yet fatal complication of Neurofibromatosis Type 1.

Neurofibromatosis Type 1 () is an autosomal dominant genetic disorder with an incidence of approximately 1 in 4,000 live births . Pulmonary arterial hypertension (PAH) is a rare but extremely life-threatening complication associated with . Timely recognition of this unusual and severe association between and PAH is imperative in prolonging the survival in this specific patient population.

Administration of 5-HT-1B agonist ameliorates pseudodementia induced by depression in rats.

Major depressive disorder (MDD) is the leading cause of memory impairment in general population. The serotonin hypothesis provides a target model for the treatment of depression and depression-associated memory loss. 5-HT-1B receptor is suggested as a potential candidate in the pathophysiology of depressive illness.

Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity.

Nephroprotective potential of selenium and taurine against mercuric chloride induced nephropathy in rats.

The study was aimed to estimate whether pre-treatment with sodium selenite or taurine would reverse kidney damage induced by intraperitoneal injection of mercuric chloride in rats. Animals were divided into six groups: (1) control group; (2) sodium selenite group; (3) taurine group; (4) HgCl2 group; (5) sodium selenite pretreated group; (6) taurine pretreated group. The results demonstrated that HgCl2 causes significant enhancement in serum malondialdehyde (MDA), creatinine, N-acetyl-beta-d-glucosaminidase (NAG), cystatin C, nephrin and interleukin 6 (IL-6) levels accompanied with significant reduction in serum nitric oxide (NO) level.

Modulation of anticancer drug-induced P-glycoprotein expression by naringin.

Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumour cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (P-gp) on the surface of tumour cells, thereby reducing drug cytotoxicity. In the present study, naringin (the predominant flavonone found in grapefruit and other related citrus species) was tested for its potential ability to modulate the expression of P-gp in a short-term animal bioassay, in comparison with verapamil (a calcium channel blocker and positive MDR reversal agent).

Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene.

The effects of various doses of lycopene were studied in streptozotocin (STZ)-induced hyperglycaemic rats to evaluate its possible hypoglycaemic, hypolipidaemic and antioxidant activity in diabetes. Compared to the normoglycaemic group, the treatment of rats with a single dose of STZ (65 mg/kg body weight) revealed a significant increase (p<0.05) only in plasma hydrogen peroxide (H(2)O(2)), i.

Effect of environmental lead pollution on blood lead levels in traffic police constables in Islamabad, Pakistan.

Objective: To determine the blood lead levels and trace elements (copper and manganese) in traffic police constables in Islamabad in order to assess the effects of environmental pollution on the levels of metals in body fluids.

Methods: Blood samples were collected from 47 male traffic police constables, 21 to 45 years of age, posted in different areas of Islamabad and controlling traffic from 3 months to 18 years, 8 hours/day, 6 days/week. Adolescent males (13-19 years), residing in comparatively clean and very low traffic areas were included as controls.

Impact of weather on presentation of kidney tumour: a thirteen years retrospective study.

Objective: Presentation of kidney tumor patients in-group gave birth to the hypothesis that oncogen exposure is influenced by the weather. Frequency and spectrum of renal tumors was also studied. Incidence of the tumor cannot be evaluated as we are lacking in data collection of pediatric population, inoperable cases and patients with bilateral renal tumors, who did not under go nephrectomies.

Serum IgE levels in patients with allergic problems and healthy subjects.

Total serum IgE levels were estimated in 219 patients with various allergic disorders (119 with bronchial asthma, 68 with allergic rhinitis and 32 with urticaria) and 240 healthy age matched subjects. Serum IgE levels were significantly (P < 0.001) higher in healthy males (mean 181 IU/ml) than females (mean 99 IU/ml).

Blood lead levels in young children in Chakshahzad, Islamabad.

Blood lead levels were estimated in one hundred and seventy school children, aged 13 to 19 years, residing in Chakshahzad area of Islamabad. The overall mean blood lead level was 2.38 ug/dl (range 0.

Diagnosis of pleural effusions.

Sixty patients of pleural effusion with different aetiology are described. Various microbiological and biochemical parameters were done simultaneously in blood and pleural fluid to differentiate tuberculosis and non-tuberculosis effusions. Some biochemical tests were thought to be helpful in differential diagnosis but no single parameter was found diagnostic.

Immunoglobulins and serum proteins in toxoplasmosis.

Immunoglobulin levels in 47 children (age 13-20 years) with toxoplasmosis were compared with 46 age and sex matched controls. No significant difference was observed in mean serum immunoglobulin (IgG, IgA, IgM) levels between patients and controls but mean IgM levels were significantly (P) higher in children with acute toxoplasma infection. Total proteins were higher in patients while mean albumin and globulin levels were similar between the two groups.

Iron deficiency in adolescents.

Two hundred and seventy school children between 13 to 20 years were investigated for iron deficiency. Overall iron deficiency (assessed by serum ferritin assay) was 39% in adolescents; 30% boys and 54% girls were iron depleted, anemia was found in 17% boys (Hb 13g/dl) and in 18% girls (Hb 12g/dl). Iron deficiency was more frequent than anemia in adolescent girls than boys.

Seroepidemiology of toxoplasma gondii infection in young school children in Islamabad.

Sera, from 270 school children (age 13 to 20 years) residing in suburbs of Islamabad, were investigated for the presence of toxoplasma gondii, IgG antibodies using the enzyme linked immunosorbent assay (ELISA). The overall prevalence was 17.4%.

Protein electrophoresis in tuberculosis.

Serum electrophoresis was done in 31 patients with pulmonary tuberculosis and 62 age and sex matched controls. Protein values amongst controls were higher than those described by others. In tuberculosis there was significant decrease in total proteins, and albumin with corresponding increase in globulin, mainly due to an increase in gamma globulin fraction.