Coding roles of long non-coding RNAs in breast cancer: Emerging molecular diagnostic biomarkers and potential therapeutic targets with special reference to chemotherapy resistance

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes

Oncogenic and Tumor Suppressive Components of the Cell Cycle in Breast Cancer Progression and Prognosis

Cancer, a disease of inappropriate cell proliferation, is strongly interconnected with the cell cycle. All cancers consist of an abnormal accumulation of neoplastic cells, which are propagated toward uncontrolled cell division and proliferation in response to mitogenic signals. Mitogenic stimuli include genetic and epigenetic changes in cell cycle regulatory genes and other genes which regulate the cell cycle. This suggests that multiple, distinct pathways of genetic alterations lead to cancer development. Products of both oncogenes (including cyclin-dependent kinase (CDKs) and cyclins) and tumor suppressor genes (including cyclin-dependent kinase inhibitors) regulate cell cycle machinery and promote or suppress cell cycle progression, respectively. The identification of cyclins and CDKs help to explain and understand the molecular mechanisms of cell cycle machinery. During breast cancer tumorigenesis, cyclins A, B, C, D1, and E; cyclin-dependent kinase (CDKs); and CDK-inhibitor proteins p16, p21, p27, and p53 are known to play significant roles in cell cycle control and are tightly regulated in normal breast epithelial cells. Following mitogenic stimuli, these components are deregulated, which promotes neoplastic transformation of breast epithelial cells. Multiple studies implicate the roles of both types of components—oncogenic CDKs and cyclins, along with tumor-suppressing cyclin-dependent inhibitors—in breast cancer initiation and progression. Numerous clinical studies have confirmed that there is a prognostic significance for screening for these described components, regarding patient outcomes and their responses to therapy. The aim of this review article is to summarize the roles of oncogenic and tumor-suppressive components of the cell cycle in breast cancer progression and prognosis

Prevalence, drug susceptibility pattern of Klebsiella pneumoniae in women with urinary tract infection

Background- Urinary tract infection (UTI) is an infection in which bacteria enters the tract and cultivate in the urinary tract i.e. the kidneys, ureters, bladder, and urethra. It is a common type of infection affecting females. UTI in case of K. Pneumoniae (gram – bacteria) is symptomatic with signs of increase in urinary frequency, urgency, suprapubic discomfort, and dysuria are all common symptoms.Materials and Methods- We recruited 80 female patients diagnosed with UTI of different ages for the study. The study population was female patients aged 18-45yrs, n=50 (group 1) and 55-85yrs, n=30 (group 2) who were hospitalized for symptoms of urinary tract infections. Midstream urine is collected in sterile containers. Samples were treated within 2 hours of collection in cysteine-lactose electrolyte deficiency (CLED) medium. Colony count, morphology, Gram stain, and biochemical characteristics were used to identify UTI-positive isolates. The disc diffusion method was used to test antibiotic susceptibility in both age groups, and the results were compared.&nbsp

Association of vitamin-D with hypothyroidism in adult female patients in north Indian population

Background: Thyroid disorder is found to be most commonly occurring endocrine disorder in females. Thyroid hormones have an imperative position in metabolic methods in human body, and several physiological and pathological stimuli are known to influence thyroid metabolism. The increased incidence of hypovitaminosis D was diagnosed in population with hypothyroidism. Objective: To check the relation of Vitamin D in adult female patients diagnosed with hypothyroidism. Method: We recruited 60 patients and divided these patients into two groups, Group-1- Hypothyroidism patients (n=30) and Group-2- Control patients (n=30). Thyroid-Stimulating Hormone (TSH), total Triiodothyronine (T3), total Thyroxine (T4), and Vitamin D levels were estimated by automated method in Abbott ARCHITECT ci8200 machine. Results: In the present study we found patients with hypothyroidism 73.3% (n=22) has low level of Vitamin D while 26.6% (n=8) of population have normal level of Vitamin D. We could not find significant association between Vitamin D and hypothyroidism (p>0.05). Conclusion: Our study concluded that hypothyroidism has no significant role in lowering the levels of Vitamin D but we also emphasize the fact that Vitamin D should be done as routine investigation in healthy as well as hypothyroidism patients as its value was also less in control subjects

Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential

Despite advancements in healthcare facilities for diagnosis and treatment, cancer remains the leading cause of death worldwide. As prevention is always better than cure, efficient strategies are needed in order to deal with the menace of cancer. The use of phytochemicals as adjuvant chemotherapeutic agents in heterogeneous human carcinomas like breast, colon, lung, ovary, and prostate cancers has shown an upward trend during the last decade or so. Flavonoids are well-known products of plant derivatives that are reportedly documented to be therapeutically active phytochemicals against many diseases encompassing malignancies, inflammatory disorders (cardiovascular disease, neurodegenerative disorder), and oxidative stress. The current review focuses on two key flavonols, fisetin and quercetin, known for their potential pharmacological relevance. Also, efforts have been made to bring together most of the concrete studies pertaining to the bioactive potential of fisetin and quercetin, especially in the modulation of a range of cancer signaling pathways. Further emphasis has also been made to highlight the molecular action of quercetin and fisetin so that one could explore cancer initiation pathways and progression, which could be helpful in designing effective treatment strategies

Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements

Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed

Prevalence, Drug Susceptibility Pattern of Klebsiella Pneumoniae in Women with Urinary Tract Infection

Background- Urinary tract infection (UTI) is an infection in which bacteria enters the tract and cultivate in the urinary tract i.e. the kidneys, ureters, bladder, and urethra. It is a common type of infection affecting females. UTI in case of K. Pneumoniae (gram – bacteria) is symptomatic with signs of increase in urinary frequency, urgency, suprapubic discomfort, and dysuria are all common symptoms.Materials and Methods- We recruited 80 female patients diagnosed with UTI of different ages for the study. The study population was female patients aged 18-45yrs, n=50 (group 1) and 55-85yrs, n=30 (group 2) who were hospitalized for symptoms of urinary tract infections. Midstream urine is collected in sterile containers. Samples were treated within 2 hours of collection in cysteine-lactose electrolyte deficiency (CLED) medium. Colony count, morphology, Gram stain, and biochemical characteristics were used to identify UTI-positive isolates. The disc diffusion method was used to test antibiotic susceptibility in both age groups, and the results were compared.&nbsp