High CD44 immunoexpression correlates with poor overall survival: Assessing the role of cancer stem cell markers in oral squamous cell carcinoma patients from the high-risk population of Pakistan

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment naïve OSCC. The immunoreactivity for each marker was correlated with patient clinicopathologic characteristics, oral cancer risk chewing habits, and survival. The minimum follow-up time for all patients was five years, and survival estimates were calculated using the Kaplan-Meier method and Cox proportional hazards model. Results. In this cohort of 100 patients, there were 57 males and 43 females. The median OS and DFS time durations observed were 64 and 52.5 months, respectively. Positive expression for CD44, CD133, L1CAM, and SOX2 was observed in 33%, 23%, 41%, and 63% of patients. High CD44 expression correlated with decreased OS (P=0.047) but did not influence DFS. However, CD133, L1CAM, and SOX2 had no effect on either OS or DFS. Tonsils, nodal involvement, and AJCC stage were independent predictors of worse OS and DFS both. Conclusion. Of the CSC markers investigated here, only CD44 was a predictor for poor OS. CD44 was also associated with advanced AJCC and T stages. Interestingly, CD133 was significantly lower in patients who habitually consumed oral cancer risk factors

Biotransformation of oral contraceptive ethynodiol diacetate with microbial and plant cell cultures

<p>Abstract</p> <p>Background</p> <p>Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate (<b>1</b>) by using plant and microbial cultures.</p> <p>Results</p> <p>The biotransformation of ethynodiol diacetate (<b>1</b>) with <it>Cunninghamella elegans</it> and plant cell suspension cultures of <it>Ocimum basilicum</it> and <it>Azadirachta indica</it> is being reported here for the first time. Biotransformation of <b>1</b> with <it>Cunninghamella elegans</it> yielded three new hydroxylated compounds, characterized as 17α-ethynylestr-4-en-3β,17β-diacetoxy-6α-ol (<b>2</b>), 17α-ethynylestr-4-en-3β,17β-diacetoxy-6β-ol (<b>3</b>), and 17α-ethynylestr-4-en-3β,17β-diacetoxy-10β-ol (<b>4</b>) and a known metabolite, 17α-ethynyl-17β-acetoxyestr-4-en-3-one (<b>5</b>). The biotransformation of <b>1</b> with <it>Ocimum basilicum</it> included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17α-ethynyl-17β-acetoxyestr-4-en-3-one (<b>5</b>), 17α-ethynyl-17β-hydroxyestr-4-en-3-one (<b>6</b>), 17α-ethynyl-3 β-hydroxy-17β-acetoxyestr-4-ene (<b>7</b>) and 17α-ethynyl-5α,17β-dihydroxyestr-3-ene (<b>8</b>). Biotransformation of <b>1</b> with <it>Azadirachta indica</it> culture yielded compounds <b>5</b> and <b>6</b>. Spectroscopic data of compound <b>8</b> is being reported for the first time. Structure of compound <b>6</b> was unambiguously deduced through single-crystal x-ray diffraction studies.</p> <p>Conclusion</p> <p>Biotransformation of an oral contraceptive, ethynodiol diacetate (<b>1</b>), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.</p

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Aims: Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy. Methods: The European Society of Cardiology PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: 1) women without hypertension (‘PPCM-noHTN’); 2) women with hypertension but without pre-eclampsia (‘PPCM-HTN’); 3) women with pre-eclampsia (‘PPCM-PE’). Maternal (6-month) and neonatal outcomes were compared. Results: Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (NYHA IV in 44.4% and 29.9%, p&lt;0.001), more frequent signs of heart failure (pulmonary rales in 70.7% and 55.4%, p=0.002), higher baseline LVEF (32.7% and 30.7%, p=0.005) and smaller left ventricular end diastolic diameter (57.4mm [±6.7] and 59.8mm [±8.1], p&lt;0.001). There were no differences in the frequencies of death from any cause, re-hospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF≥50%) (adjusted OR 2.08 95% CI 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted OR 2.84 95% CI 1.66-4.87). Conclusion: Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM