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Objective: To determine the frequency of mutations in exon 11 of the c-kit gene in patients with leukemia. Material and Methods: The study included 50 leukemia patients (31 with acute myeloid leukemia, 5 with acute lymphoblastic leukemia, 9 with chronic myeloid leukemia, and 5 with chronic lymphocytic leukemia) that underwent PCR-SSCP, followed by direct DNA sequencing. Results: In all, 28 of the leukemia patients were male and 22 were female, with a mean age of 31.88 years (range: 2-65 years). In total, 20 mutations in 19 patients were identified, including Lys550Asn, Tyr568Ser, Ile571Thr, Thr574Pro, Gln575His, Tyr578Pro, Asp579His, His580Gln, Arg586Thr, Asn587Asp, and Arg588Met, as well as novel point mutations at codons Ile563Lys, Val569Leu, Tyr570Ser, and Pro577Ser. Ue571Leu substitution was observed in 2 patients and Trp582Ser substitution was observed in 3 patients. Conclusion: The results suggest that mutations in exon 11 of the c-kit gene might be useful as molecular genetic markers for leukemia [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs are small non-coding RNAs that regulate gene expression at multiple levels. The discovery of virally encoded miRNAs attracted immense attention towards their role in viral replication and pathogenesis. Kaposi''s-sarcoma-associated herpes virus encodes miRNA that functions as an orthologue of human cellular miRNA, i.e., hsa-miR-155. Keeping the same view we extended the miRNA-homology search between the miRNAs of humans and Epstein–Barr virus. The In silico analyses shows that EBV encoded miR-BART-5 has a significant ‘seed’ sequence homology to hsa-miR-18 of humans. Further, the mRNA transcripts of the human genes involved in cellular growth could potentially be targeted by both viral as well as human miRNAs. The known etiological role of hsa-miR-18 as an oncomiR suggests that miR-BART-5 may function as viral oncomiR as observed in EBV-positive gastric carcinoma patients. [Copyright &y& Elsevier]

Background: Pharmacokinetic (PK) studies suggest that talazoparib is primarily eliminated unchanged via renal excretion. The current study investigated how varying degrees of renal impairment may affect the PK of talazoparib, and evaluated the safety and tolerability of talazoparib, in patients with advanced solid tumors with/without renal impairment. Methods: Patients with advanced solid tumors and normal renal function or different degrees of renal impairment measured by estimated glomerular filtration rate (eGFR: mild = 60–89, moderate = 30–59, severe = 15–29 mL/min/1.73 m2) were enrolled in this open-label, non-randomized, phase I study. Talazoparib was administered orally at 0.5 mg/day for 22 days. Primary PK parameters included the area under the plasma concentration-time curve from 0 to 24 h (AUC0–24) and maximum observed plasma concentration (Cmax) at steady state (Day 22). Safety and tolerability were also investigated. Results: Thirty-four patients were enrolled. At Day 22, compared with patients with normal renal function (n = 9), patients with mild (n = 9), moderate (n = 8), or severe (n = 8) renal impairment had a 12.2%, 43.0%, and 163.3% increase in talazoparib AUC0–24, and a 11.1%, 31.6%, and 89.3% increase in talazoparib Cmax, respectively. Talazoparib was generally well tolerated, and overall there were no notable differences in the treatment-emergent adverse event profile across renal function groups. Conclusions: Exposure to talazoparib increased with worsening renal impairment. Overall, this study confirms current dosing recommendations in patients with mild and moderate renal impairment (1 mg/day and 0.75 mg/day, respectively) and indicates that a lower starting dose of 0.5 mg/day should be considered for patients with severe renal impairment. Clinical Trials Registration: NCT02997163. [ABSTRACT FROM AUTHOR]

The single-arm, multicenter, phase 2 GIBB study (NCT02320487) investigated bendamustine plus obinutuzumab (BG) in previously untreated CLL. Patients (N = 102) received six cycles of intravenous obinutuzumab (cycle [C] 1: 100 mg day 1/900 mg day 2, and 1000 mg days 8/15; C2–6 1000 mg day 1) plus bendamustine (C1 90 mg/m2 days 2/3; C2–6 days 1/2). Complete response (CR), the primary endpoint, was 50%, overall response 89%. Estimated 2-year progression-free survival (PFS) and overall survival (OS) were 86% and 97%, respectively. Following initial minimal residual disease (MRD) negativity, median MRD negativity duration was 28.9 months. Undetectable MRD (<10−4) was observed in up to 83% of evaluable patients in peripheral blood (any time) and 59% in bone marrow at response evaluation. Most common grade 3/4 adverse events (AEs) were neutropenia (25%; 5% febrile) and infusion-related reactions (9%). BG proved clinically active in CLL with high response, MRD negativity, and survival rates, consistent with other first-line studies of anti-CD20 antibody/bendamustine combinations. [ABSTRACT FROM AUTHOR]

Purpose More than 1 million new occurrences of cancer are diagnosed in India annually. Among patients with cancer, pain is a common and persistent symptom of the disease and its treatment. However, few studies to date have evaluated the prevalence of pain and the adequacy of pain management in Indian hospitals. This cross-sectional study aimed to assess the prevalence and sociodemographic patterns of cancer pain and pain management among a sample of inpatients and newly registered outpatients at four large regional cancer centers in India. Methods A sample of 1,600 patients with cancer who were current inpatients or newly registered outpatients were recruited and administered a questionnaire that was based on the Brief Pain Inventory. The survey tool included questions on demographics, medical history, and extent of clinical pain experienced. In addition, a pain management index score was created to link the severity of cancer pain with medication prescribed to treat it. Results A total of 88% of patients reported pain in the past 7 days, and approximately 60% reported that their worst pain was severe. Several demographic and medical characteristics of the study population predicted severe pain, including the following: lower educational level, outpatient status, and debt incurred as a result of illness. A total of 67% of patients were inadequately treated with analgesics. Inadequate pain management was associated with both treatment hospital and patient type, and patients who reported debt as a result of their illness were more likely to have inadequate pain management. Conclusion A majority of Indian patients with cancer experience significant pain and receive inadequate pain management. Improvement of pain management for Indian patients with cancer is needed urgently. [ABSTRACT FROM AUTHOR]

Purpose: More than 1 million new occurrences of cancer are diagnosed in India annually. Among patients with cancer, pain is a common and persistent symptom of the disease and its treatment. However, few studies to date have evaluated the prevalence of pain and the adequacy of pain management in Indian hospitals. This cross-sectional study aimed to assess the prevalence and sociodemographic patterns of cancer pain and pain management among a sample of inpatients and newly registered outpatients at four large regional cancer centers in India. Methods: A sample of 1,600 patients with cancer who were current inpatients or newly registered outpatients were recruited and administered a questionnaire that was based on the Brief Pain Inventory. The survey tool included questions on demographics, medical history, and extent of clinical pain experienced. In addition, a pain management index score was created to link the severity of cancer pain with medication prescribed to treat it. Results: A total of 88% of patients reported pain in the past 7 days, and approximately 60% reported that their worst pain was severe. Several demographic and medical characteristics of the study population predicted severe pain, including the following: lower educational level, outpatient status, and debt incurred as a result of illness. A total of 67% of patients were inadequately treated with analgesics. Inadequate pain management was associated with both treatment hospital and patient type, and patients who reported debt as a result of their illness were more likely to have inadequate pain management. Conclusion: A majority of Indian patients with cancer experience significant pain and receive inadequate pain management. Improvement of pain management for Indian patients with cancer is needed urgently. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with higher-risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have demonstrated activity in patients with MDS and in vitro synergy with azacitidine.Methods: A phase 2 randomized, placebo-controlled clinical trial of azacitidine and pracinostat was conducted in patients who had International Prognostic Scoring System intermediate-2-risk or high-risk MDS. The primary endpoint was the complete response (CR) rate by cycle 6 of therapy.Results: Of 102 randomized patients, there were 51 in the pracinostat group and 51 in the placebo group. The median age was 69 years. The CR rate by cycle 6 of therapy was 18% and 33% (P = .07) in the pracinostat and placebo groups, respectively. No significant differences in overall survival (median, 16 vs 19 months, respectively; hazard ratio, 1.21; 95% confidence interval, 0.66-2.23) or progression-free survival (11 vs 9 months, respectively; hazard ratio, 0.82; 95% confidence interval, 0.546-1.46) were observed between groups. Grade ≥3 adverse events occurred more frequently in the pracinostat group (98% vs 74%), leading to more treatment discontinuations (20% vs 10%).Conclusions: The combination of azacitidine with pracinostat did not improve outcomes in patients with higher-risk MDS. Higher rates of treatment discontinuation may partially explain these results, suggesting alternative dosing and schedules to improve tolerability may be required to determine the potential of the combination. Cancer 2017;123:994-1002. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m2 or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up. [ABSTRACT FROM AUTHOR]

Effective capping activity of lithiated sarcosine TFSI on the formation of single crystalline SrTiO3 nanocubes via hydrothermal method has been investigated. Lithiated sarcosine TFSI formation by zwitterionic transformation was confirmed by NMR and FTIR studies. 13C and 7Li NMR studies showed the stabilization of metal hydroxide anions by the secondary ammonium cations (-NH2+-) of lithiated sarcosine. The FESEM results revealed the formation of SrTiO3 nanocubes. TEM images showed the spherical and square shaped defects within the round edged cubic particles with the average size of 90 nm and SAED pattern indicates the single crystalinity. The crystalinity and nanocubic shape of SrTiO3 were strongly influenced by lithiated sarcosine TFSI. Hence, we propose lithiated sarcosine TFSI as an effective capping agent for the synthesis of single crystalline SrTiO3 nanocubes. [ABSTRACT FROM AUTHOR]

Abstract: A secondary amine based ionic liquid, lithiated sarcosine-trifluoromethyl sulfonyl imide (TFSI) solution has been developed for hydrothermal synthesis of hexagonal ZnO micro rods. The ionic liquid formation was confirmed by 13C-NMR, 7Li-NMR and FTIR analysis and a possible mechanism was proposed for the formation of wurtzite hexagonal ZnO micro rods using morphological observations. The lithiated sarcosine TFSI solution has shown both capping and catalytic activities in bringing out the hexagonal ZnO micro rods. [Copyright &y& Elsevier]

Background: The diagnosis of Pott's disease is mostly based on clinicoradiological observations substantiated by the bacterial culture, staining and histopathology. Since, no single technique is enough to conclude Pott's disease in diagnosis, the present study was undertaken to correlate the clinicoradiological, microbiological, histopathological and molecular method to evaluate the effectiveness in diagnosis of Pott's disease. Materials and Methods: 62 clinicoradiologically suspected cases of Pott's disease were included in this study. The specimens for diagnostic work up were collected either during surgery or by computed tomography guided fine needle aspiration. All these specimens were tested for tuberculosis (TB) through Ziehl-Neelsen (ZN) microscopy, BACTEC culture, histopathology and polymerase chain reaction (PCR). The final diagnosis was established by the results of performed tests and clinicoradiological improvement of cases at the end of 6 months on anti tubercular treatment. Results: Out of 62 cases, 7 were excluded from this study as these were turned out to be neoplastic lesions on histopathology. Amongst remaining 55 cases, the TB was diagnosed in 39 (71%) on histopathology, 37 (67.5%) on PCR, 27 (49%) on BACTEC culture and 20 (36.3%) on ZN microscopy. Ultimately 45 cases were tested as positive and 10 were detected as negative for TB in combination of ZN microscopy, BACTEC culture and histopathology. PCR was positive in 37 of 45 cases and 10/55 cases remained negative. On clinical analysis of these 10 cases, it was noted that these were cases of relapse/poor compliance. The combination of PCR and histopathology was also shown positive for TB in 45 cases. Hence, the PCR showed a fair positive agreement (Κc = 0.63) against the combined results of all performed traditional methods. Conclusions: The combination of PCR and histopathology is a rapid and efficient tool for diagnosis of Pott's disease. [ABSTRACT FROM AUTHOR]

Acute Myeloid Leukemia (AML)-M0 is a cancer of blood-forming cells in the bone marrow. KIT gene is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. We have designed this study aiming to identify and determine the frequency and prevalence of mutations in North Indian patients suffering from AML-M0. To perceive the KIT gene mutations, we have carried out PCR-SSCP followed by direct DNA sequencing in 50 AML-M0 cases. We have found eight cases (24.2%) with t(8;21) having 12 point mutations whereas three cases (17.6%) with inv(16) having four point mutations. The point mutation detected at exon 9 in five cases is Asp496Val. Eight different point mutations were identified at exon 11 in seven AML-M0 cases that include Lys550Asn, Tyr568Ser, Ile571Leu, Tyr578Pro, Trp582Ser and Arg588Met. Point mutations at codons Ile571Leu and Trp582Ser was found in two independent cases. Three point mutations were found in exon 17 (Leu813Pro, Lys818Arg, Val825Ala) in three AML-M0 cases. The results underline that the KIT gene appears to be most frequently mutated target in AML-M0 cases. These observations suggest that mutations in exon 11 of the KIT gene might be useful molecular genetic markers in AML-M0 and these mutations might be related to progression and clinical pathogenesis [ABSTRACT FROM AUTHOR]

The breast tuberculosis (TB) is an extremely rare manifestation for the reason that mammary cells offer great resistance to the survival and multiplication of Mycobacterium infection. The diagnosis is difficult because of nonspecific clinical and radiological findings. It is usually suspected in a multiparous, reproductive woman. We report three cases of tubercular infection of breast confirmed by either mycobacteriology, pathology or both. We described their diagnostic confirmation and six month follow-up after antitubercular treatment (ATT). [ABSTRACT FROM AUTHOR]

Human genomic DNA from 90 cases of acute myeloid leukemia (AML) were screened for mutations in the c-kit gene. C-kit is a receptor tyrosine kinase class III that is expressed by early hematopoietic progenitor cells and plays crucial role in hematopoietic stem cell proliferation, differentiation and survival. Exon 8 and 17 are the frequent sites of mutations in the leukemia cases. To determine the spectrum of mutations at exon 8 and 17 of c-kit gene in 90 acute myeloid leukemia AML cases, we have done Polymerase Chain Reaction (PCR) Single-strand conformational polymorphism (SSCP) followed by DNA sequencing. The c-kit mutation frequencies in exon 8 were 25.55% (23/90) and in exon 17 were 34.44% (31/90) in AML cases. We have detected two contrary deletions Tyr 418del and Asp 419del in exon 8 in 23 cases and three point mutations that is Asp816Val, Asp820Gly and Asn822Lys in exon 17, in 31 cases; respectively. Each and every mutations detected in our study are located in region of the receptor's extracellular domain and intracellular domain of second catalytic region. It gives the impression that incidence of mutation at exon 8 and 17 is elevated and possibly involved in clinical pathogenesis of AML and utilizable tool as the molecular prognostic marker. [ABSTRACT FROM AUTHOR]

The present work describes the synthesis of a Schiff base, 3-{4-[4-(benzylideneamino) benzenesulfonyl]phenyl}-2-phenylquinazolin-4(3H)-one from a novel quinazolinone, 3-[4-(4-aminobenzenesulfonyl)phenyl]-2-phenylquinazolin-4(3H)-one. The quinazolinone was prepared by reacting 2-phenyl-4H-3,1-benzoxazin-4-one with dapsone. The structure of the synthesized Schiff base is confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. [ABSTRACT FROM AUTHOR]

Heminasal aplasia is a rare congenital malformation. It is often associated with other malformations of the facial region, including abnormalities of the eye and lacrimal system, facial bone malformations and proboscis lateralis. We present two cases of heminasal aplasia, discuss their embryological basis and nasal reconstruction of the same. [ABSTRACT FROM AUTHOR]