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Tehseen, M.

Publications and source records attributed to Tehseen, M..

2 recordsLinked to original sources

Elevated soluble Galectin-3 as a marker of chemotherapy efficacy in Breast cancer patients: a prospective study

PurposeGalectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3. MethodsBreast cancer patients with first time cancer diagnosis and no prior treatment (n=88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA respectively. Healthy women (>18 years of age, n=63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease free survival analysis. ResultsEnhanced levels of plasma (adjuvant) and stromal (neo-adjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion. ConclusionThe findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors post chemotherapy can also be used to predict long term prognosis in patients. Key pointsIncreased Gal-3 secretion due to chemotherapy leads to better prognosis and longer disease-free survival. The analysis of soluble Gal-3 expression could be useful as a support tool in predicting treatment efficacy in patients with no visible tumor remaining for follow up through imaging.

cancer biology

Structure of the processive human Pol δ holoenzyme

In eukaryotes, DNA polymerase {delta} (Pol {delta}) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol {delta}-DNA-PCNA complex in the absence and presence of FEN1. Pol {delta} is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol {delta}s activity in replicating the human genome.

biochemistry