Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer

A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency. Using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but its drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RARα and treats APL in cell and animal models and human patients. ATRA-induced Pin1 ablation also inhibits triple negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors

FARMERS’ PERCEPTION ON THE EFFECTS AND MANAGEMENT OF SALINE WATER ON SOIL AND CROPS WITHIN KILIFI AND KWALE COUNTIES

Coastal Kenya is arid and semi-arid. Farmers in coastal Kenya use saline borehole irrigation water for crop production. There is limited information regarding the perception of farmers on effect and management of salinity on crop production. This study assessed farmers’ perception on effects and management of saline water on soil and crops in coastal Kenya. The study was carried out in Kilifi County (Kaloleni, Magarini and Kilifi sub-Counties) and Kwale County (Msambweni and Matuga sub-Counties). A purposive sampling procedure was used to select farmers from the two study sites. Farmers owning boreholes and practicing irrigated agriculture for at least three calendar years were selected per site resulting in a sample size of 30 farmers from each county. Data were obtained from sampled farmers through interviews and structured questionnaires. The farmers’ survey was undertaken using a single - visit survey approach. Data collected were divided into four subsections, which include, socio-demographic profiles, farmers’ sources of information on crop production, history of borehole water, crops grown and soil and water management. Survey data were coded and analyzed using SPSS software, version 14. Data were analyzed using descriptive statistics. Results revealed that all (100 %) household size in Kilifi County and 92.2 % of Kwale County consisted of four or less members, showing that the smaller household sizes depended on irrigated crop production either for food or income generation. Radio was the most common means of communication (Kilifi 90 % and Kwale 87.5 %) through national and vernacular languages. Farmers in Kilifi County (93.3 %) and Kwale County (86.7 %) did not belong to any agricultural society. This meant that some farmers lacked information on the advantages and how agricultural societies are formed. Farmers growing crops under irrigation in Kwale County obtained water from boreholes. Farmers in both counties never tested the quality of borehole water used to irrigate their crops. All farmers (100 %) in Kwale County and 86.7 % in Kilifi County reported gradual decline in yield, 13.3 % of famers in Kilifi County reported stunted growth, 84.6 % of farmers from Kilifi County and 78.6 % from Kwale County reported that salts in irrigation water (indicated by white residues on soil after irrigation) accumulate in soil over time that degraded the soil and harmed plants. Farmers in both counties (Kilifi 84.6 % and Kwale 64.3 %) use manure during planting to manage their soils

FARMERS’ PERCEPTION ON THE EFFECTS AND MANAGEMENT OF SALINE WATER ON SOIL AND CROPS WITHIN KILIFI AND KWALE COUNTIES

Coastal Kenya is arid and semi-arid. Farmers in coastal Kenya use saline borehole irrigation water for crop production. There is limited information regarding the perception of farmers on effect and management of salinity on crop production. This study assessed farmers’ perception on effects and management of saline water on soil and crops in coastal Kenya. The study was carried out in Kilifi County (Kaloleni, Magarini and Kilifi sub-Counties) and Kwale County (Msambweni and Matuga sub-Counties). A purposive sampling procedure was used to select farmers from the two study sites. Farmers owning boreholes and practicing irrigated agriculture for at least three calendar years were selected per site resulting in a sample size of 30 farmers from each county. Data were obtained from sampled farmers through interviews and structured questionnaires. The farmers’ survey was undertaken using a single - visit survey approach. Data collected were divided into four subsections, which include, socio-demographic profiles, farmers’ sources of information on crop production, history of borehole water, crops grown and soil and water management. Survey data were coded and analyzed using SPSS software, version 14. Data were analyzed using descriptive statistics. Results revealed that all (100 %) household size in Kilifi County and 92.2 % of Kwale County consisted of four or less members, showing that the smaller household sizes depended on irrigated crop production either for food or income generation. Radio was the most common means of communication (Kilifi 90 % and Kwale 87.5 %) through national and vernacular languages. Farmers in Kilifi County (93.3 %) and Kwale County (86.7 %) did not belong to any agricultural society. This meant that some farmers lacked information on the advantages and how agricultural societies are formed. Farmers growing crops under irrigation in Kwale County obtained water from boreholes. Farmers in both counties never tested the quality of borehole water used to irrigate their crops. All farmers (100 %) in Kwale County and 86.7 % in Kilifi County reported gradual decline in yield, 13.3 % of famers in Kilifi County reported stunted growth, 84.6 % of farmers from Kilifi County and 78.6 % from Kwale County reported that salts in irrigation water (indicated by white residues on soil after irrigation) accumulate in soil over time that degraded the soil and harmed plants. Farmers in both counties (Kilifi 84.6 % and Kwale 64.3 %) use manure during planting to manage their soils

Pharmacotherapy for Conjunctival Malignancies

Medical therapy for ocular malignancies is an expanding field with increasing options for ocular surface malignancies. Epithelial, lymphoproliferative, and pigmented lesions of the conjunctiva now all have pharmacologic therapeutic options at the clinician’s disposal. Topical chemotherapy drops of interferon alpha-2b (IFNα-2b), 5-fluorouracil, and mitomycin have shown promising results as a primary therapy for ocular surface squamous neoplasia (OSSN). They have also been used as adjuvants to surgical excision. While these agents are the main medical agents for OSSN, retinoic acid, aloe vera, cidofovir, and anti-vascular endothelial growth factor have been tried with some success. Pharmacological therapy for ocular and adnexal lymphoma is dependent on whether the disease is localized (unilateral or bilateral) or systemic. Local therapy has traditionally been radiotherapy, but local injections of rituximab and interferon have shown some success in small series. Systemic disease is treated with systemic chemotherapies, including monoclonal antibodies and radio-tagged monoclonal agents. Pigmented lesions of the conjunctiva are life threatening, and surgery remains the mainstay of treatment. In cases of unresectable disease, and as adjuvants, medical therapies are needed. Mitomycin has an effect against pigmented cells. While imperfect, it reduces ocular surface pigmentation. The use of IFNα-2b has been reported with less success. Novel checkpoint inhibitors targeting programed cell death 1 (PD-1), such as pembrolizumab, have shown early potential for pigmented lesions of the ocular surface, but additional data is needed to understand their role in conjunctival melanoma