A novel coexistence of tetrasomy 8 and FLT3-ITD along with variant 3 way translocation t(4;17;15) in acute promyelocytic leukemia: Case study and literature review.

Here, we report a case of Acute promyelocytic leukemia (APL) with three way complex translocation involving chromosomes 4, 15, and 17. Although chromosome 4 is most commonly associated chromosome in three way translocation, present case is the first report with four novel co-existent findings of new break point region on chromosome 4, new cyclic mechanism with simultaneous breaks, presence of a co-existent tetrasomy 8 and FLT3 ITD positivity.; Comprehensive assessment highlight the utility of combining morphology, immunophenotyping, karyotyping, fluorescence in situ hybridization, and molecular studies for better characterization, optimal management of APL with a better understanding of the pathogenic mechanism and prognosis of the disease.

Specific Chromosomal Aberrations in Primary Amenorrhoea: Study on 3776 Cases from Indian Population.

OBJECTIVE: To verify the prevalence of chromosomal abnormalities in women with primary amenorrhoea in India aiming at appropriate genetic counselling. METHODS: In a 16-year retrospective (2001-2016) study, 3776 women with primary amenorrhoea were evaluated. Chromosomal analysis of all the cases was done by GTG banding. Clinical history and other laboratory findings were taken into consideration to determine the diagnosis. RESULTS: The karyotype results revealed 31.2% cases with chromosomal abnormalities (n = 1177/3776). In patients with abnormal chromosome complement, 31.2% exhibited numerical aberrations (n = 367) and 34.9% with structural aberrations (n = 411). About 33.9% of cases were with XY male karyotype (n = 399). CONCLUSION: As per the literature till date, this study is the largest with high incidence of chromosomal abnormalities; early detection of abnormalities is necessary for guidance to reproductive management and genetic counselling.

X-autosome translocations in amenorrhoea: a report of a three way translocation from Indian population.

Chromosomal translocations have been reported in a number of women undergoing cytogenetic studies for amenorrhoea and gonadal dysgenesis. This study was taken up to emphasize the role of X chromosome and to know the frequency of X-autosomal translocations in women with amenorrhoea in Indian population. Cytogenetic analysis was carried out in 1567 subjects referred for amenorrhoea during the period 2002-2012. GTG-banding was performed from peripheral blood lymphocyte cultures to detect the chromosome abnormalities in all the cases. The karyotype results revealed 43.6% cases with chromosomal abnormalities (n = 683 of 1567 cases). The X-autosomal translocations was found in 2.64% (n = 18 of 683 cases). The common chromosomes involved with X were chromosomes 2, 4, 14 and 20. The translocations involved both p and q arms of the X chromosome.The break point "q26" of X was observed in the majority of the cases. Two interesting cases are discussed: one with three way translocation and another with two translocations. A high number of primary amenorrhoea (PA) and secondary amenorrhoea (SA) cases were involved in X-auto translocation which clearly reveals that chromosomal analysis plays an important role in the evaluation of amenorrhoea.

Scrotal hemangioma: a case report.

We report a case of scrotal-hemangioma in a 14-year-old boy. Subcutaneous scrotal-perineal hemangioma may mimic an inguinal hernia, thus forming a diagnostic and therapeutic challenge. Histopathological study confirms the diagnosis. Definitive treatment by en bloc excision is recommended.

Perspectives on chemopreventive and therapeutic potential of curcumin analogs in medicinal chemistry.

Curcumin is a natural polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over past 50 years has indicated that this polyphenol is highly pleiotropic molecule capable of preventing and treating various cancers. The anticancer potential of Curcumin is severely affected by its limited systemic and target tissue bioavailability and rapid metabolism. In the present review article, we provide a summarized account of different drug delivery systems employed for tackling the problem of cucumin's bioavailability such as liposomes, phospholipid complexes and nanoparticles. Concomitantly we have reviewed the large volume of literature reports describing structural modifications of Curcumin and the anticancer potential of its analogs. Some of the difluorocurcumin analogs allowing longer circulation times and preferential accumulation in the pancreas seem to offer promising leads for conducting first in-depth animal studies and subsequently clinical trials for the use of these analogs for prevention of tumor progression and/or treatments of human malignancies.

Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice.

PURPOSE: The purpose of the current study was to assess the effect of newly synthesized Curcumin analogs on COX-2 protein by molecular docking studies and by assessments of the effect of one such analog (CDF) on nuclear factor NF-kappaB and PGE(2). In addition, we have determined the pharmacokinetics and tissue distribution of CDF in mice compared to Curcumin. METHODS: Molecular docking on COX-2 protein was assessed by standard computer modeling studies. PGE(2) assay in conditioned media was done utilizing high sensitivity immunoassay kit following manufacturer's instructions, while NF-kappaB was done by routine EMSA. Serum pharmacokinetics and tissue distribution studies were carried out using the validated high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. RESULTS: The molecular docking showed that fluorocurcumin analogs do not introduce any major steric changes compared to the parent Curcumin molecule, which was consistent with down-regulation of NF-kappaB and reduced PGE(2) levels in cells treated with CDF. Pharmacokinetic parameters revealed that CDF had better retention and bioavailability and that the concentration of CDF in the pancreas tissue was 10-fold higher compared to Curcumin. CONCLUSION: Our observations clearly suggest that the bioavailability of CDF is much superior compared to Curcumin, suggesting that CDF would be clinically useful.

New difluoro Knoevenagel condensates of curcumin, their Schiff bases and copper complexes as proteasome inhibitors and apoptosis inducers in cancer cells.

PURPOSE: Emerging evidence clearly suggests the potential chemopreventive and anti-tumor activity of a well known "natural agent" curcumin. However, studies have shown that curcumin is not readily bioavailable, and thus the tissue bioavailability of curcumin is also poor except for gastrointestinal track. Because of the potential biological activity of curcumin, many studies have attempted for making a better analog of curcumin that is equally effective or better with increased bioavailability, which was the purpose of our current study. METHODS: We have designed and synthesized new difluoro Knoevenagel condensates of curcumin and Schiff bases along with their copper (II) complexes and evaluated their biological activities with respect to the inhibitory effects on purified rabbit 26S proteasome, and growth inhibition and induction of apoptosis in colon and pancreatic cancer cell lines. RESULTS: All copper complexes possess distorted square planar geometries with 1:1 metal to ligand stoichiometry with reversible copper redox couple. The difluoro compound CDF exhibited inhibitory effects on purified rabbit 20S proteasome or cellular 26S proteasome, and caused both growth inhibition of cancer cell lines and induced apoptotic cell death in our preliminary assessment. CONCLUSION: Our results suggest that our newly synthesized classes of curcumin analogs could be useful as chemopreventive and/or therapeutic agents against cancers.

Cytogenetic profile of acute lymphocytic leukemia patients: report of a novel translocation t(4;13) (q21 x 3; q35) from an Indian population.

Acute lymphocytic leukemia (ALL) is a malignant neoplasm characterized by clonal proliferation, decreased apoptosis and accumulation of immature lymphoid cells in the bone marrow as well as the peripheral blood. The aim of this study was to determine the overall cytogenetic profile of Indian ALL patients along with their frequency and distribution pattern. A total of 75 ALL subjects were included in the study. The major outcome of the work was identification of a novel translocation t(4;13) (q21 x 3;q35) that has not yet been reported. In addition, a few rare chromosomal aberrations such as t(4;16) (p16;q12 x 2) and t(7;10)(q36;q21 x 2) were also detected. Overall, of 75 cases, 67 (89 x 33%) were successfully karyotyped. Normal and abnormal karyotypes were seen in 38 (56 x 7%) and 29 (43 x 3%) cases respectively. Various other abnormalities were hyperdiploidy (20 x 68%), hypodiploidy (10 x 34%), t(8;14) (3 x 44%), t(9;22) (6 x 9%), t(4;16) (3 x 44%), t(7;10) (3 x 44%) and gain of chromosome 8, 13, 16, and 22 was seen in one case each (3 x 44%). Deletions in chromosome 5, 9 and 11 were found to be 3 x 44, 6 x 89 and 6 x 89% respectively, while complex and other aberrations were detected in 3 x 44 and 13 x 8% cases. Finally, we conclude that cytogenetic analysis has an important role in routine genetic diagnostic workup and management of ALL patients.

Cytogenetic investigations in couples with repeated miscarriages and malformed children: report of a novel insertion.

Recurrent miscarriage and the birth of a malformed child continue to be challenging problems for the patient and clinician. Often, cytogenetic studies have an important role in the evaluation of couples with a poor obstetric history. The present study deals with analysis of chromosome abnormalities in 2150 couples from India, and is the largest group ever reported in the literature. The observed incidence of chromosomal rearrangements in these couples was 3.5%. Apart from reciprocal, Robertsonian, inversions, a unique case of chromosome insertion was identified, which is perhaps only the second report in literature. Minor chromosome variants such as inv(9),inv(Y),9qh+, D/G variants were observed in 108 subjects. Cytogenetic studies should be performed for all couples with repeated miscarriages and bad obstetric history, and in cases of detected chromosomal aberration, the patient should be counselled individually according to the type of anomaly.

Cytogenetic investigation in chronic myeloid leukemia: study from an Indian population.

Chronic myeloid leukemia (CML) is a malignant neoplasm of hematopoietic cells characterized by abnormal proliferation of myeloid precursors, decreased rates of self destruction and an arrest in cellular differentiation. The bone marrow and peripheral blood accumulates all forms of mature and immature granulocytes, primarily blast cells. It is the most common type of leukemia seen in India, accounting for 30% of all leukemias. Cytogenetic analysis plays a vital and important role in the diagnosis of CML patients. The present study consists of cytogenetic evaluation of 175 CML cases from the Indian population with ages ranging from 6-86 years (mean of 42.8). The study population included 115 males (65.72%) and 60 females (34.28%) with a Male: Female ratio 1.9:1. Out of the 175 cases, 164 (93.7%) were successfully karyotyped while culture failure was observed for 11 (6.3%). Among the 164 reported cases, 53 (32.3%) showed a normal karyotype while within the 111 (67.7%) abnormal cases, 96 cases (86.5%) showed the presence of Philadelphia (Ph') chromosome with standard translocation t(9;22); Ph'+ve along with secondary aberrations was detected in 9 (8.1%) cases. Variants of Ph' chromosome were detected in only one case (0.9%). Ph'-ve CML with other chromosomal aberrations were detected in 5 (4.5%) cases, including +8, del 20q, del 11q and marker chromosome. Furthermore, we believe that availability of more advanced molecular techniques can be used as a supportive tool in CML diagnosis even though it cannot fully replace cytogenetics, which remains the backbone for laboratory investigation of the disease.