Resistance to receptor-blocking therapies primes tumors as targets for HER3-homing nanobiologics

Resistance to anti-tumor therapeutics is an important clinical problem. Tumor-targeted therapies currently used in the clinic are derived from antibodies or small molecules that mitigate growth factor activity. These have improved therapeutic efficacy and safety compared to traditional treatment modalities but resistance arises in the majority of clinical cases. Targeting such resistance could improve tumor abatement and patient survival. A growing number of such tumors are characterized by prominent expression of the human epidermal growth factor receptor 3 (HER3) on the cell surface. This study presents a “Trojan-Horse” approach to combating these tumors by using a receptor-targeted biocarrier that exploits the HER3 cell surface protein as a portal to sneak therapeutics into tumor cells by mimicking an essential ligand. The biocarrier used here combines several functions within a single fusion protein for mediating targeted cell penetration and non-covalent self-assembly with therapeutic cargo, forming HER3-homing nanobiologics. Importantly, we demonstrate here that these nanobiologics are therapeutically effective in several scenarios of resistance to clinically approved targeted inhibitors of the human EGF receptor family. We also show that such inhibitors heighten efficacy of our nanobiologics on naïve tumors by augmenting HER3 expression. This approach takes advantage of a current clinical problem (i.e. resistance to growth factor inhibition) and uses it to make tumors more susceptible to HER3 nanobiologic treatment. Moreover, we demonstrate a novel approach in addressing drug resistance by taking inhibitors against which resistance arises and re-introducing these as adjuvants, sensitizing tumors to the HER3 nanobiologics described here

Evidence-based national vaccine policy

India has over a century old tradition of development and production of vaccines. The Government rightly adopted self-sufficiency in vaccine production and self-reliance in vaccine technology as its policy objectives in 1986. However, in the absence of a full-fledged vaccine policy, there have been concerns related to demand and supply, manufacture vs. import, role of public and private sectors, choice of vaccines, new and combination vaccines, universal vs. selective vaccination, routine immunization vs. special drives, cost-benefit aspects, regulatory issues, logistics etc. The need for a comprehensive and evidence based vaccine policy that enables informed decisions on all these aspects from the public health point of view brought together doctors, scientists, policy analysts, lawyers and civil society representatives to formulate this policy paper for the consideration of the Government. This paper evolved out of the first ever ICMR-NISTADS national brainstorming workshop on vaccine policy held during 4-5 June, 2009 in New Delhi, and subsequent discussions over email for several weeks, before being adopted unanimously in the present form

Resistance to receptor-blocking therapies primes tumors as targets for HER3-homing nanobiologics

Resistance to anti-tumor therapeutics is an important clinical problem. Tumor-targeted therapies currently used in the clinic are derived from antibodies or small molecules that mitigate growth factor activity. These have improved therapeutic efficacy and safety compared to traditional treatment modalities but resistance arises in the majority of clinical cases. Targeting such resistance could improve tumor abatement and patient survival. A growing number of such tumors are characterized by prominent expression of the human epidermal growth factor receptor 3 (HER3) on the cell surface. This study presents a “Trojan-Horse” approach to combating these tumors by using a receptor-targeted biocarrier that exploits the HER3 cell surface protein as a portal to sneak therapeutics into tumor cells by mimicking an essential ligand. The biocarrier used here combines several functions within a single fusion protein for mediating targeted cell penetration and non-covalent self-assembly with therapeutic cargo, forming HER3-homing nanobiologics. Importantly, we demonstrate here that these nanobiologics are therapeutically effective in several scenarios of resistance to clinically approved targeted inhibitors of the human EGF receptor family. We also show that such inhibitors heighten efficacy of our nanobiologics on naïve tumors by augmenting HER3 expression. This approach takes advantage of a current clinical problem (i.e. resistance to growth factor inhibition) and uses it to make tumors more susceptible to HER3 nanobiologic treatment. Moreover, we demonstrate a novel approach in addressing drug resistance by taking inhibitors against which resistance arises and re-introducing these as adjuvants, sensitizing tumors to the HER3 nanobiologics described here

A Quantitative Approach to Innovation in Agricultural Value Chains: Evidence from Kenyan Horticulture

In less developed countries such as Kenya, trade is increasingly occurring through, and employment is found within, global and local value chains. Yet, although innovation is widely recognised as crucial for development, the endogenous relationship between small-scale innovations and participation in global value chains (GVCs) has yet to be explored sufficiently. This endogeneity is highlighted using the 3L’s of labels, linkages and learnings as key overlapping factors that affect both the processes of innovation as well as GVC participation. Drawing on a survey of 320 fresh fruit farmers and 55 interviews in Kenya, we develop a novel method to quantify small-scale agricultural innovations, which are categorised into two overarching types. The first, formal, emanate from meeting standard requirements; the second, informal, evolve from local contexts and are less codified. We find that GVC farmers perform more formal innovations, while local farmers perform similar levels of informal innovation to GVC farmers

Contribution of Microbe-Mediated Processes in Nitrogen Cycle to Attain Environmental Equilibrium

Nitrogen (N), the most important element, is required by all living organisms for the synthesis of complex organic molecules like amino acids, proteins, lipids etc. Nitrogen cycle is considered to be the most complex yet arguably important cycle next to carbon cycle. Nitrogen cycle includes oxic and anoxic reactions like organic N mineralization, ammonia assimilation, nitrification denitrification, anaerobic ammonium oxidation (anammox), dissimilatory nitrate reduction to ammonium (DNRA), comammox, codenitrification etc. Nitrogen cycling is one of the most crucial processes required for the recycling of essential chemical requirements on the planet. Soil microorganisms not only improve N-cycle balance but also pave the way for sustainable agricultural practices, leading to improved soil properties and crop productivity as most plants are opportunistic in the uptake of soluble or available forms of N from soil. Microbial N transformations are influenced by plants to improve their nutrition and vice versa. Diverse microorganisms, versatile metabolic activities, and varied biotic and abiotic conditions may result in the shift in the equilibrium state of different N-cycling processes. This chapter is an overview of the mechanisms and genes involved in the diverse microorganisms associated in the operation of nitrogen cycle and the roles of such microorganisms in different agroecosystems