Emergence, Growth and Management of Slums around the Globe with a Special Focus on Pakistan

In the past few decades, the world has witnessed massive urbanization to access better living standards including better employment, education and health opportunities. This urbanization trend ends in the emergence and growth of informal settlements and highlights the urban dualism. This rapid urbanization amounts to the crisis of housing, employment opportunities and other basic facilities. In this regard, this study is an effort to provide the baseline understanding of slums of developing countries in general and Pakistan specifically. It also attempts to provide the definition of slums and the actual status of slums across the globe with a special focus on developing countries. Socioeconomic and living conditions of the slum dwellers in developing regions are also explored in this study. This also concludes that the status of slum residents need proper recognition, identification and mapping for the improvements in their living standards and provision of public facilities. It also provides some ways to identify the slum dwellers and mapping of slums in urban peripheries of Pakistan.

Modulation of Proliferation and Apoptosis Biomarkers in Oral and Other Cancers

Cancer, also known as neoplasia, involves uncontrolled cell proliferation leading to malignant tumor formation. Epithelial cancers (or carcinomas, representing about 80% of all cancers) are a group of cancers originating in the epithelial lining of many locations, such as digestive tract, airways, breast, reproductive tracts and oral cavity. Oral cancer is one of the eight most common types of cancer worldwide. It starts from the upper digestive tract, including the larynx, oral and nasal cavities. Whereas lung cancer is the major cause of cancer-related deaths worldwide, representing about 26% to 28% per year. Heavy alcohol consumption, betel nut chewing, smoking, viral infections, occupation hazard and exposure to UV radiation are the major risk factors. Tyrosine kinase receptors (TKs), such as EGFR and Lyn are major regulators of cell growth and survival. In cancer cells, such receptors are constitutively activated and lead to malignant phenotype. Blocking of active TKs efficiently stops proliferation and induces apoptosis in oral and lung cancer cells. In the present study, we selected five TKIs (Genistein, Gefitinib, Erlotinib, Dasatinib, and Imatinib) which acts upon EGFR and Src family tyrosine kinases. Imatinib and Dasatinib are non-optimal TKIs for oral and lung carcinomas, and have to be utilized at relatively high concentrations to display inhibition. Our goal was to select therapeutically suitable small molecules, such as resveratrol (a natural polyphenol) and artemisinin along with its derivatives (synthetic endoperoxides) to potentiate the sub-optimal activity of standard TKIs. The objective of our study was to investigate standard TKIs and the possible adjuvant effects of artemisinin derivatives (endoperoxides, EPs) and resveratrol (natural phenol, NP) on highly malignant lung cancer cells (NCI-H460) and laryngeal cancer cells (KCLB-SNU46) of lower malignancy. Optimal combinations of TKIs and EPs/NP that decrease the proliferative capacity of oral and lung cancer cell lines, and increase their apoptosis potential were thus investigated. The techniques employed were flowcytometry, spectrophotometry, SDS-PAGE and western blotting. Out of five TKIs, Imatinib and Dasatinib at higher concentration and on 48 hours incubation affected the oral cancer cell line (KCLBSNU46). However, the lung cancer cell line (NCI-H460) responded to Gefitinib as well as Imatinib and Dasatinib only after 48 hours. Artemisinin itself didn’t show any effect but its endoperoxide derivatives OD59 and OD66 showed potent anticancer activity (with very low IC50) in both cell lines when compared to that of the standard TKIs. Resveratrol showed no effect on oral cancer cells, but lung cancer cells did respond to high resveratrol concentrations. In combination studies, resveratrol and endoperoxides (OD66 and OD67) showed significant synergistic effects when combined with gefitinib and dasatinib at very low concentrations in both the cell lines. Furthermore it was confirmed that these synergistic combinations induced apoptosis by modulating the phosphorylation of the EGFR and Lyn tyrosine kinases. This study conclude that resistance phenomena in cancer cells can be modulated by combining sub-therapeutic doses of standard TKIs with least effective doses of natural and synthetic compounds. This approach can conveniently reduce the dosage as well as the cytotoxic effects of the clinically used TKIs on cancer patients.