Highly Air‐Stable Thieno[3,2‐b]thiophene‐Thiophene‐Thiazolo[5,4‐d]thiazole‐Based Polymers for Light‐Emitting Diodes

A series of highly air‐stable, low‐bandgap poly(3‐alkylthiophene)s containing electron‐rich thieno[3,2‐b]thiophene and electron‐deficient thiazolo[5,4‐d]thiazole rings were synthesized by the Stille coupling reaction. The polymers exhibited good thermal stability and solubility with excellent film forming properties when drop‐ or spin‐cast from solution. A strong absorption at 564–568 nm and a shoulder at 614–616 nm were observed. The optical bandgap of the polymers was found to be 1.82–1.85 eV. The IP of the polymers was found to be 5.62–5.65 eV. All polymers showed strong fluorescent emission both in solution and in the solid state. EL devices were fabricated using the polymers as an emissive layer and red emission was observed with the emission range of 649–679 nm.

     

Primary Hodgkin's disease of spleen--a case report

Primary malignant lymphoma of spleen is rare with primary Hodgkin's disease (HD) of spleen being rarer. The diagnosis of primary splenic HD is usually made on the histopathological examination of the splenectomy specimen. We report an interesting case of primary HD of spleen in a child emphasizing its rarity and the role of fine needle aspirate cytology in early diagnosis and non-surgical management of this entity.     

Absence of pathogenic calcium sensing receptor mutations in sporadic idiopathic hypoparathyroidism

BACKGROUND: Sporadic idiopathic hypoparathyroidism (SIH) is the most common cause of hypoparathyroidism. While calcium sensing receptor (CaSR) autoantibodies are observed in 49% of cases, aetiopathogenetic mechanisms in others are under investigation. Mutations in the PTH gene including its 3' untranslated region, autoimmune regulator gene and lead CTLA-4 gene single nucleotide polymorphism (SNPs) are not associated with the disease. There are reports of de novo activating mutations of the CaSR gene in a few patients with SIH. OBJECTIVE: To assess the frequency of CaSR mutations in patients with SIH. SUBJECTS AND METHODS: DNA sequencing of all six translating exons and nine of 12 intron/exon boundaries of the CaSR gene was performed by Sangers dideoxy chain termination method using an automated sequencer in 39 patients with SIH. Spot urinary calcium/creatinine ratio in the fasting state and ultrasonography of the abdomen was performed to assess hypercalciuria and nephrolithiasis. The PCR-RFLP analysis was performed using Hin1II restriction endonuclease in 32 additional patients with SIH and 90 healthy controls to further assess the prevalence of a novel missense SNP observed in the DNA sequencing. RESULTS: Nucleotide sequence analysis revealed the presence of a wild type CaSR gene in all subjects, except in one patient who showed a missense mutation (Val621Met) due to substitution of base G-->A in the heterozygous state at position 79877 in exon 7 (codon 621) coding for the first transmembrane loop of the CaSR. The V621M polymorphism was confirmed by PCR-RFLP and was due to a maternal allele. However, the mother and brother of this patient with the same SNP were asymptomatic and had normal serum chemistry indicating the functionally inert nature of the polymorphism. None of the additional 32 patients with SIH and 90 controls showed V621M SNP. The urinary calcium/creatinine ratio and ultrasonography were normal in all patients with SIH. CONCLUSION: De novo activating mutation of the CaSR gene typical of familial hypoparathyroidism is not common among patients with SIH in India.     

First-trimester reference centiles of fetal biometry in Indian population

Aim and objective: To create crown-rump length (CRL)-based biometric chart for fetus in the first trimester among the Indian population.

Material and methods: Cross-sectional data were obtained from 400 singleton pregnancies between 11 and 14 weeks gestation with a normal outcome. Linear regression models were constructed; the mean and SD were derived as a function of CRL.

Results: There was a positive correlation of CRL with nuchal translucency (NT) (y?=?0.0102x?+?0.6307 R^2?=^?0.1177), biparietal diameter (BPD) (BPD?=?0.032*CRL +0.185 R^2?=^?0.765), occipito-frontal diameter (OFD), lateral ventricular diameter (LV), abdominal circumference (AC) (AC?=?0.944*CRL +9.684 R^2?=^?0.668), femur length (FL) (FL?=?0.222*CRL ?4.734 R^2?=^?0.661), fetal weight (FW) (FW?=?1.328*CRL ?10.41 R^2?=^?0.662). The regression models and centile charts of NT, BPD, OFD, LV, AC, and FW were constructed. Taking FW as the independent variable, a linear equation of BPD, AC, and FL to calculate weight was constructed.

Conclusions: The first-trimester centile charts of fetal parameters can be used as a reference for Indian population in the determination of gestational age or other adverse outcomes.     

A phase II study of gemcitabine,carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer

Purpose

The doublet gemcitabine and carboplatin is effective for the treatment of recurrent ovarian cancer, while multi-agent chemotherapy with bevacizumab may add additional benefit. This phase II study tested the efficacy and safety of a biweekly gemcitabine, carboplatin, and bevacizumab combination in patients with platinum-sensitive recurrent ovarian, peritoneal, or tubal cancer (ROC).

Patients and methods

Eligible patients received concurrent gemcitabine 1000 mg/m², carboplatin area under the curve 3, and bevacizumab 10 mg/kg administered intravenously on days 1 and 15 every 28 days for six cycles or up to 24 cycles if clinical benefit occurred. The primary end points were progression-free survival (PFS) by RECIST, and safety; the secondary end points were objective response rates and overall survival.

Results

Overall, 45 patients were enrolled. The median PFS was 13.3 months (95% CI, 11.3 to 15.3). The objective response rate was 69%. Grade 4 hematologic toxicities included neutropenia (27%) and thrombocytopenia (2%). Grades 3 and 4 non-hematologic toxicities included fatigue (18%), pain (9%), and nausea/vomiting (4%). There were 2 episodes of cerebrovascular accidents, 2 noted DVTs, and no episodes of bowel perforation. Median OS was 36.1 months (95% CI, 26.7 to 45.5).

Conclusion

Biweekly gemcitabine, carboplatin, and bevacizumab were an effective regimen in recurrent ovarian cancer, with comparable toxicity to recently reported day 1 gemcitabine, carboplatin, bevacizumab, and day 8 gemcitabine. Response rate and PFS are improved from reported outcomes of the gemcitabine carboplatin doublet. The degree to which biweekly dosing may present a more rationale schedule for this triplet should be evaluated further.     

The more the messier: centrosome amplification as a novel biomarker for personalized treatment of colorectal cancers

Colon cancer is currently the third most common cancer and second most fatal cancer in the United States, resulting in approximately 600,000 deaths annually. Though colorectal cancer death rates are decreasing by about 3% every year, disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis, the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments. Colon carcinogenesis is notably a slow process that can take decades. Known factors that contribute to the development of colon cancer are mutational, epigenetic and environmental, and risk factors include age, history of polyps and family history of colon cancer. Colorectal cancers exhibit heterogeneity in their features and are often characterized by the presence of chromosomal instability, microscopic satellite instability, or CpG island methylator phenotype. In this review, we propose that centrosome amplification may be a widespread occurrence in colorectal cancers and could potently influence tumor biology. Moreover, the quantitation of this cancer-specific anomaly could offer valuable prognostic information and pave the way for further customization of treatment based on the organellar profile of patients. Patient stratification models that take into account centrosomal status could thus potentially reduce adverse side effects and result in improved outcomes for colorectal cancer patients.     

Radiologic–Pathologic Correlation of Hepatocellular Carcinoma Treated with Chemoembolization

To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre- and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa (κ) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have ≥85% specificity for predicting complete pathologic necrosis. The κ coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.     

A novel microtubule-modulating agent induces mitochondrially driven caspase-dependent apoptosis via mitotic checkpoint activation in human prostate cancer cells

Hormone-refractory prostate cancer, its skeletal metastasis and complications remain a therapeutic challenge. Here we show that treatment with (S)-3-((R)-9-bromo-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyiso-benzofuran-1(3H)-one (EM011), the brominated analogue of a plant-derived non-toxic antitussive alkaloid, noscapine, achieved significant inhibition of hormone-refractory human prostate cancer implanted intratibially in the bone as shown by non-invasive, real-time bioluminescent imaging of tumour growth in nude mice. Mechanistically, in vitro data suggested that the antiproliferative and proapoptotic effects of EM011 in human prostate cancer cell lines were through blockade of cell-cycle progression by impairing the formation of a bipolar spindle apparatus. The G2/M arrest was accompanied by activation of the mitotic checkpoint, a pre-requisite for induction of optimal apoptosis. Attenuation of mitotic checkpoint by siRNA duplexes led to a reduction in mitotic arrest and subsequent apoptosis. Our results further demonstrated participation of an intrinsic mitochondrially mediated apoptotic pathway that ultimately triggered caspase-driven EM011-induced apoptosis. EM011 did not exert any detectable toxicity in normal tissues with frequently dividing cells such as the gut and bone marrow. Thus, these data warrant further evaluation of EM011 for the management of prostate cancer.