Partial splenic embolization to permit continuation of systemic chemotherapy.

Systemic chemotherapy treatments, commonly those that comprise oxaliplatin, have been linked to the appearance of distinctive liver lesions that evolves to portal hypertension, spleen enlargement, platelets sequestration, and thrombocytopenia. This outcome can interrupt treatment or force dosage reduction, decreasing efficiency of cancer therapy. We conducted a prospective phase II study for the evaluation of partial splenic embolization in patients with thrombocytopenia that impeded systemic chemotherapy continuation. From August 2014 through July 2015, 33 patients underwent partial splenic embolization to increase platelets count and allow their return to treatment. Primary endpoint was the accomplishment of a thrombocyte level superior to 130 × 109 /L and the secondary endpoints were the return to chemotherapy and toxicity. Partial splenic embolization was done 36 times in 33 patients. All patients presented gastrointestinal cancer and colorectal malignancy was the commonest primary site. An average of 6.4 cycles of chemotherapy was done before splenic embolization and the most common regimen was Folfox. Mean platelet count prior to embolization was 69 × 109 /L. A total of 94% of patients achieved primary endpoint. All patients in need reinitiated treatment and median time to chemotherapy return was 14 days. No grade 3 or above adverse events were identified. Aiming for a 50% to 70% infarction area may be sufficient to achieve success without the complications associated with more extensive infarction. Combined with the better safety profile, partial splenic embolization is an excellent option in the management of thrombocytopenia, enabling the resumption of systemic chemotherapy with minimal procedure-related morbidity.

Tissue-specific regulation of BiP genes: a cis-acting regulatory domain is required for BiP promoter activity in plant meristems.

The binding protein BiP is an endoplasmic reticulum (ER)-resident member of the HSP70 stress-related protein family, which is essential for the constitutive function of the ER. In addition to responding to a variety of environmental stimuli, plant BiP exhibits a tissue-specific regulation. We have isolated two soybean BiP genomic clones, designated gsBiP6 and gsBiP9, and different extensions of their 5' flanking sequences were fused to beta-glucuronidase (GUS) reporter gene and introduced into Nicotiana tabacum by Agrobacterium tumefaciens-mediated transformation. Transgenic plants displayed prominent GUS activity in the vascular bundles of roots and shoots as well as in regions of intense cell division, such as procambial region and apical meristems. Promoter deletion analyses identified two cis-regulatory functional domains that are important for the spatially-regulated activation of BiP expression under normal plant development. While an AT-rich enhancer-like sequence, designated cis-acting regulatory domain 1, CRD1 (-358 to -211, on gsBiP6), activated expression of the BiP minimal promoter in all organs analyzed, BiP promoter activity in meristematic tissues and phloem cells required the presence of a second activating domain, CRD2 (-211 to -80). Apparently, the CRD2 sequence also harbors negative cis-acting elements, because removal of this region caused activation of gsBiP6 promoter in parenchymatic xylem rays. These results suggest that the tissue-specific control of BiP gene expression requires a complex integration of multiple cis-acting regulatory elements on the promoter.