Anticancer medicines in Pakistan: An analysis of essential medicines lists.

OBJECTIVE: The lack of anticancer drugs for curative and supportive purposes is the critical reason for the low survival rate in low-and-middle-income countries. This study aims to analyze whether the National Essential Medicines List (NEML) and Registered Essential Medicines List (REML) are in concordance with the World Health Organization (WHO) Essential Medicines List (EML) and whether the formularies prevalent in the country are parallel to each other and to the NEML. METHOD: An observational study design was used in which antineoplastic drugs from the 2021 NEML and REML were compared with 2021 WHO EML to evaluate their availability in Pakistan. Market access was determined. Moreover, the formularies of six different hospital types were compared with each other and with the NEML, and REML to estimate the availability within hospitals. RESULTS: There were 66 anticancer drugs in 2021 WHO EML and all were found in Pakistan's 2021 NEML but only 48 drugs (73%) were found in the REML. Hydroxycarbamide and dasatinib were two registered drugs absent in all hospitals' formularies. The market access for anticancer medicines was 73% (48 of 66). Semigovernment hospital (86%) has the highest availability, followed by the government hospital (80%). All the hospitals have unregistered drugs including bortezomib, lenalidomide, and mesna. CONCLUSION: Pakistan's NEML adopts WHO EML abruptly but all medicines are not registered. The hospitals are trying their best to increase availability but optimum drug regulations to revise NEML based on the country's requirements and emphasizing registration of anticancer medicines are needed to improve the country's availability of antineoplastic agents.

Regulation of Cell Signaling Pathways by Genistein in Different Cancers: Progress, Prospects and Pitfalls.

On the translational front, integrative genomic approaches have spurred the identification of diverse mechanisms of drug resistance, tumor heterogeneity, metastasis and emerging preclinical targets. Recent breakthroughs in oncogenic cell signaling pathways have forged new links and multi-disciplinary researchers have unraveled different facets of signaling landscapes. Natural product research has witnessed breakneck developments mainly in the context of the ever-expanding list of bioactive components having significantly pharmacological properties. Genistein has gradually gained appreciation because of its multifaceted roles in the prevention and inhibition of carcinogenesis and metastasis. More importantly, the entry of genistein into various phases of clinical trials substantiates the medicinal and pharmacological significance of genistein in cancer chemoprevention. In this review, we have attempted to summarize how genistein regulated different oncogenic pathways in carcinogenesis and metastasis. Furthermore, genistein-mediated regulation of non-coding RNAs is also an interesting feature that has been included in this review to realistically analyze how genistein-mediated control of miRNAs, lncRNAs and circRNAs influence carcinogenesis. In the later sections, we have provided a summary of clinical trials related to genistein for cancer prevention/inhibition. However, apart from the optimistic approaches to further investigate genistein-mediated cancer-inhibitory effects, certain hints have emerged which underscore the pro-metastatic role of genistein. Therefore, the pro-metastatic role of genistein in different cancers should be rationally tested in a broader context because these properties in the future may reduce the enthusiasm in the quest to pursue genistein as a potent cancer chemopreventive agent.

Amelioration of Ovalbumin-Induced Allergic Asthma by Juglans regia via Downregulation of Inflammatory Cytokines and Upregulation of Aquaporin-1 and Aquaporin-5 in Mice.

Juglans regia (J. regia) has been used traditionally to treat cough and asthma. The present study evaluates the immunomodulatory and anti-inflammatory potential of J. regia against ovalbumin (OVA)-induced allergic asthma. Intraperitoneal sensitization proceeded by intranasal challenge with OVA was used to induce allergic asthma. BALB/c mice were treated with methanol, n-hexane, and ethyl acetate extracts of J. regia and methylprednisolone one week after 2nd sensitization with OVA and continued for 7 days. mRNA expression levels of IL-4, IL-5, IL-13, AQP-1, AQP-5 TNF-α, TGF-ß, and NF-kB were determined using reverse transcription polymerase chain reaction. Hematoxylin and eosin, and periodic acidic-Schiff stains were used for histopathological studies of lung tissues. The data presented all three extracts of J. regia significantly ameliorated airway inflammation by reducing expression levels of IL-4, IL-5, and IL-13 and TNF-α in OVA-treated mice. The suppression of goblet cells hyperplasia and inflammatory cells infiltration by J. regia involved low TGF-ß and NF-kB levels. Pretreatment with J. regia also increased the AQP-1 and AQP-5 expression levels in mice treated with OVA. This study supported the traditional use of J. regia and proposed that J. regia ameliorated allergic asthma by suppression of proinflammatory cytokines and elevation of AQP-1 and AQP-5 expression levels.

Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss".

There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research.   However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.