Primary amenorrhoea - cytogenetic study in 40 Indian women.

BACKGROUND: Primary amenorrhoea (PA) refers to an ailment when adolescent girls do not attain menarche naturally. It is one of the most common gynaecological disorders specified. Chromosomal abnormalities play a pivotal role in PA. Cytogenetic analysis is an indispensable diagnostic tool to determine the abnormality of the chromosome. In an emerging country like India, cytogenetic analysis is at a nascent stage. There are very few studies on Cytogenetics present in eastern India, including West Bengal. In rural and suburban areas PA sufferers often experience late diagnosis and struggle to access suitable curative management. The aim of the study is to evaluate the various types of chromosomal abnormalities in patients suffering from PA for accurate, better management of the same and further counselling. METHODS: A total of 40 PA cases were referred by obstetricians and gynaecologists to the Department of Genetics of Nirnayan Health Care, Kolkata. To screen the chromosomal abnormalities, human leukocyte culture was accomplished with their peripheral venous blood followed by G-banding and then karyotyping was executed according to ISCN-2020. RESULT: Out of 40 patients, 29 were normal among which 46,XX was found in 70% cases (n = 28) and 46,XX,9qh + in 2.5% (n = 1). The remaining 11 showed different types of abnormalities. 45,X was found in 10% (n = 4), 46,X,i(X)(q10) in 2.5% (n = 1), 46,X,del(X)(p11.2) in 2.5% (n = 1), 46,X,del(X)(p22.1) in 2.5% (n = 1), 46,X,del(X)(q24) in 2.5% (n = 1), 46,XY in 2.5% (n = 1), mos 45,X[22]/46,Xi(X)(q.10)[8] in 2.5% (n = 1) and mos 45,X[16]/46,XY[14] (2.5%) in 2.5% (n = 1). CONCLUSION: This study indicates the importance of chromosomal study which must be included in early diagnosis of PA. Karyotyping at the appropriate phase of life will not only help in the judicial management of this disorder but will also give young girls a better lifestyle.

Primary amenorrhoea is a common gynecological disorder reported in adolescent girls, often linked to chromosomal abnormalities. In Eastern India, including West Bengal, where cytogenetic analysis is still in its nascent stage, late diagnosis and limited access to curative management are prevalent issues. A study conducted from January 2021 to May 2023 at Nirnayan Healthcare, Kolkata aimed to evaluate chromosomal abnormalities in 40 PA cases. Out of these, 28 exhibited normal karyotypes (46,XX); one patient was reported with 46,XX,9qh + which is considered a normal karyotype, while the remaining 11 revealed diverse abnormalities, including 45,X; sex reversal & several structural variations. The study underscores the significance of cytogenetic analysis in the early diagnosis of Primary Amenorrhoea. Early karyotyping not only facilitates judicious management but also ensures a better lifestyle for affected girls.

Possibilities of simulation of coronavirus SARS-CoV-2 by using light scattering approach.

Issues related to human coronavirus (SARS CoV-2) are a burning topic of research in present times. Due to its easily contagious nature, real experimentation under laboratory conditions requires a high level of biosafety. A powerful algorithm serves as a potential tool for the analysis of these particles. We attempted to simulate the light scattering from coronavirus (SARS CoV-2) model. Different images were modelled using a modified version of a Monte Carlo code. The results indicate that spikes on the viruses exhibit a significant scattering profile and that the presence of spikes during modelling contributes to the distinctiveness of the scattering profiles.

Heterochromatin extension: a possible cytogenetic fate of primary amenorrhea along with normal karyotype.

Primary amenorrhoea (PA) is considered to be one of the challenging and taxing problems for the gynaecologist. Previous studies suggested that different numerical and structural chromosome abnormalities are associated with this. Heterochromatin polymorphisms are considered to be normal variant but considering the recent research on crucial cellular effects of heterochromatin, we have aimed to find out the prevalence of heteromorphism along with other standard chromosomal abnormalities. This was an observational study which was conducted in Diamond Harbour Govt. Medical College and Hospital, West Bengal during March 2019-February 2021. Clinical features of 178 patients were noted and peripheral venous blood was taken following informed consent. This comprehensive study reveals that there are 10.11% of the females among 178 females having a heterochromatin extension which is significantly high. We hence suggest that heteromorphism may be associated with ovarian dysfunction leading to amenorrhoea as the region of heterochromatin acts as a key part in chromosome structure, histone modification and gene regulation. Analysis at the molecular level may be needed to unveil any relationship between heteromorphism and PA. Impact StatementWhat is already known on this subject? Primary amenorrhoea (PA) is a menstrual abnormality found in females with the prevalence of 1-3%. It may be associated with different types of numerical and structural chromosomal anomalies. Among them Turner's syndrome (pure and in variant form) is the commonest chromosomal aberration associated with PA. Some patients with PA are found to have a normal karyotype with heterochromatin extension on the large arm (q) of either chromosome 9 or chromosome 16. Chromosomal polymorphism with increase in heterochromatin region consists of highly repetitive sequences of satellite DNA, which normally does not encode any protein and thus considered to be a normal variant.What do the results of this study add? This comprehensive study reveals that there are 10.11% of the females among 178 females having a heterochromatin extension which is significantly high. PA and certain association of phenotypical stigmata like short stature in these patients with heterochromatin extension can be explained on the basis of histone modification and gene regulation by heterochromatin.What are the implications of these findings for clinical practice and/or further research? We will be able to know about involved transcription factors those are responsible for the histone modification directly linked to the heterochromatin extension by further molecular study. That will definitely help to find out the reason for PA as well as implementation of gene therapy in these cases.

Study of frequency and types of chromosomal abnormalities in phenotypically female patients with amenorrhea in Eastern Indian population.

AIM: This comprehensive review article aims to comprehend the frequency and prevalence of chromosomal abnormalities in both primary amenorrhea (PA) and secondary amenorrhea (SA) cases and correlating it with their phenotypes, clinical features and hormonal profiles. METHODS: Research publications on prevalence of chromosomal abnormalities in both PA and SA cases worldwide and its etiology, clinical features, hormonal profiles; their correlation with chromosomal profiles were searched for on the internet, including general search engines and respective scientific sites. Only published, relevant and authentic data conducted on phenotypically female patients were considered. Another aspect of amenorrhea occurs due to several clinical conditions apart from cytogenetic viewpoint were not considered or discussed in detail. RESULTS: As literature study suggests; considering various etiology of amenorrhea counting anatomic defect of the hypothalamus or genetic defect, and various acquired causes of chromosomal anomalies contribute to be one of the major etiologies of both PA and SA; ranging from 15.9% to 63.3% in case of PA and from 3.9% to 44.4% in case of SA. In spite of the presence of any other factors responsible condition, the genetic factors need to be emphasized, which might include single gene disorders or chromosomal disorders. Individuals with chromosomal anomalies reported a wide range of abnormalities in phenotypes, as well as in other clinical features and hormonal profiles. CONCLUSION: This comprehensive review is the first structured review article that encompasses the cytogenetic profile of the amenorrhea cases and correlating it with their phenotypes, clinical features and hormonal profiles from Eastern India.

Papillary muscles of left ventricle-Morphological variations and it's clinical relevance.

INTRODUCTION: The two left ventricular papillary muscles are small structures at sternocostal and inferior wall but are vital to mitral valve competence. Extra papillary muscles could be found. Partial or complete rupture, complicating acute myocardial infarction, causes severe or even catastrophic mitral regurgitation, potentially correctable by surgery. Detailed knowledge of normal anatomy and variations is vital for accurate interpretation of information by echocardiography and for surgical repair. MATERIALS AND METHODS: The material for present study consisted of 52 formalin fixed adult apparently normal cadaveric hearts belonging to either sex obtained from the Department of Anatomy. These hearts were dissected carefully to open the left ventricle and to expose the papillary muscles. According to their attitudinal position they were described as supero-lateral (S-L) and inferoseptal muscle (I-S) instead of conventional anterolateral and posteromedial. Different morphological features of papillary muscles were noted and measurements were taken. RESULTS: Classical picture of left ventricular papillary muscle was found only in 25% cases. Additionally extra muscles were found 34.61% and 71.15% in S-L and I-S group, respectively. Different shapes and pattern of papillary muscles were also been identified. An additional attribute of this study was measurement of length and breadth of papillary muscles which thus provides a base line data for further detailed studies in a large scale. CONCLUSION: Oriental nomenclature is necessary not only for anatomist but also for electrocardiographers. Breadth of papillay muscle should be taken into morphometric account as for screening of hypertrophic cardiomyopathy. Proper anatomical knowledge is crucial for clinicians, surgeons and radiologists.

Papillary muscles of right ventricle-morphological variations and its clinical relevance.

INTRODUCTION: Papillary muscle plays an important role in stabilizing the position of the tricuspid valve. Several pathologies can result in anatomical and functional abnormalities of the papillary muscles. The aim of the study is to deliberate the morphometry of papillary muscles in tricuspid valve and to analyze with the eminent research works previously done. MATERIALS AND METHODS: The study was carried out in 52 formalin-fixed adult apparently normal cadaveric hearts belonging to either sex obtained from the Department of Anatomy. These hearts were dissected carefully to open the right ventricle and to expose the papillary muscles. Different morphological features of papillary muscles were noted, and measurements were taken. RESULT: The classical picture of three papillary muscles existed in 23.07% of the specimens. Anterior papillary muscle was in all hearts, but posterior and septal muscle was off in 15.38% and 55.76%, respectively. Double and triple papillary muscles were seen too. Anterior and posterior muscle appeared predominantly flat-top and arose from the middle third (mostly), while septal muscle was chiefly conical and originated basically from the upper third of the ventricular wall. Chordopapillary relationship with tricuspid valve leaflets was beyond conventional. Mean length and breadth of anterior muscle were 2.19±0.59 cm and 0.76±0.26 cm, those of posterior muscle were 1.39±0.63 cm and 0.67±0.43 cm, and those of septal papillary muscle were 0.95±0.38 cm and 0.59±0.09 cm. CONCLUSIONS: Detailed knowledge of normal and variable anatomy of papillary muscles is not only necessary for better understanding of tricuspid pathologies but also valuable for successful newer surgical approaches in cardiac treatment.

PARP1 depletion induces RIG-I-dependent signaling in human cancer cells.

DNA Damage Response (DDR) and DNA repair pathways are emerging as potent, ubiquitous suppressors of innate immune signaling in human cells. Here, we show that human cells surviving depletion of the Single Strand Break (SSB) repair protein PARP1 undergo p21-dependent senescence or cell cycle checkpoint activation in the context of activation of innate immune signaling, or viral mimicry. Specifically, we observe induction of a large number of interferon-stimulated genes (ISGs) and multiple pattern recognition receptors (PRRs; including RIG-I, MDA-5, MAVS, TLR3 and STING) and increased nuclear IRF3 staining. Mechanistically, depletion of the double-stranded RNA (dsRNA) helicase RIG-I or its downstream effector MAVS specifically rescues ISG induction in PARP1-depleted cells, suggesting that the RIG-I/MAVS pathway is required for sustained ISG expression in this context. Experiments with conditioned media or a neutralizing antibody to the α/ß-IFN receptor revealed that persistent ISG expression additionally requires an autocrine/paracrine loop. Finally, loss of PARP1 and radiation-induced DNA damage strongly synergize in the induction of p21 and ISGs. Overall, these findings increase our understanding of how PARP1 may suppress deleterious phenotypes associated to aging, inflammation and cancer in humans.

Cytogenetic analysis of patients with primary amenorrhea in Eastern India.

Amenorrhea is the absence of menstruation in women of reproductive age. Previous reports suggest that chromosomal abnormality is the second most common cause of amenorrhoea. Early referral for cytogenetic evaluation is recommended for the identification of underlying chromosomal aberrations in amenorrhoea patients. This was an observational study which was conducted in Vivekananda Institute of Medical sciences, Kolkata, during January 2013-December 2015. This study aims to estimate the frequency and types of chromosomal abnormalities in primary amenorrhoea (PA) patients in Eastern India and correlate their hormonal profile with chromosomal reports. Clinical features of 150 patients were recorded with clinical expertise. Peripheral venous blood was taken following informed consent, followed by karyotyping for chromosomal analysis. Results revealed 76.1% of PA with normal female karyotype (46, XX) and 23.9% with different abnormal karyotypes. Among the abnormal karyotype constituents, 50% numerical abnormalities, most frequent being Turner syndrome, pure (n = 12, 8%) and mosaic (n = 5, 3.3%). Three cases (2%) showed male (XY) karyotype. The other cases showed X structural abnormalities. This study emphasises the need for cytogenetic analysis as integral part of the diagnostic protocol in case of PA for precise identification of chromosomal abnormalities and for appropriate management and counselling of these patients.

Imaging of Programmed Cell Death Ligand 1: Impact of Protein Concentration on Distribution of Anti-PD-L1 SPECT Agents in an Immunocompetent Murine Model of Melanoma.

Programmed cell death ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy that target immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects. Recently, we developed an antibody-based PD-L1-targeted SPECT agent-111In-diethylenetriaminepentaacetic acid (DTPA)-anti-PD-L1-to identify PD-L1-positive tumors in vivo. To best use such PD-L1-targeted imaging agents, it is important, as a first step, to understand how the signal is affected by different parameters. Methods: We evaluated the impact of protein concentration on the distribution of 111In-DTPA-anti-PD-L1 in a murine model of aggressive melanoma. Results:111In-DTPA-anti-PD-L1 (dissociation constant, 0.6 ± 0.1 nM) demonstrated increased uptake in B16F10 tumors at protein concentrations equaling or exceeding 1 mg/kg at 24 h and 3 mg/kg at 72 h. At 24 h, the PD-L1-rich spleen and lungs demonstrated decreasing uptake with increasing protein concentration. At 72 h, uptake in the thymus was significantly increased at protein concentrations of 3 mg/kg or greater. Both time points demonstrated increased tracer amounts remaining in circulation as the amount of cold antibody was increased. Conclusion: These studies demonstrate that 111In-DTPA-anti-PD-L1 is capable of identifying tumors that overexpresses PD-L1 and monitoring the impact of PD-L1-rich organs on the distribution of anti-PD-L1 antibodies.

Study of arsenic exposure in oral/oropharyngeal carcinoma in West Bengal.

OBJECTIVES: To study any possible correlation between arsenic toxicity and the development of oral carcinoma in West Bengal population. MATERIAL AND METHODS: Ethical clearance for this study was obtained from the Vivekananda Institute of Medical Sciences. Out of 30 785 patients attending our hospital from November 2012 to July 2015, 107 cases and 50 control individuals were selected. The hair and buccal smear samples were obtained upon their consent for the purpose of the analysis of arsenic count and cytogenetic damage, respectively. RESULTS: Ninety-six percent of cases came from the highly arsenic affected districts and 81.3% showed their arsenic count above the safe limit (0.8 µg/g) whereas 96% of the controls' arsenic count was within the safe limit. The study showed a significant difference of the micronuclei and apoptosis frequency between the cases and controls. CONCLUSIONS: The difference of micronuclei and apoptosis frequency between cases and controls was significant. The maximum number of cases came from highly arsenic affected areas and a higher percentage of cases showed elevated arsenic count, as compared to controls, which may indicate a possible link between arsenic toxicity and this disease. However, a larger sample size is required for a proper correlation. Int J Occup Med Environ Health 2017;30(2):271-279.

Integration-free erythroblast-derived human induced pluripotent stem cells (iPSCs) from an individual with Ataxia-Telangiectasia (A-T).

Peripheral blood was obtained from a 12-year old male carrying bialleleic inactivating mutations at the ATM locus, causing Ataxia-Telangiectasia (A-T). Blood erythroid cells were briefly expanded in vitro and induced pluripotent stem cells (iPSCs) were generated via transfection with episomal vectors carrying hOCT4, hSOX2, hKLF4, hMYC and hBCL2L1. SF-003 iPSCs were free of genomically integrated reprogramming genes, had the specific compound heterozygous mutations, stable karyotype, expressed pluripotency markers and formed teratomas in immunodeficient (NOD scid gamma; NGS) mice. The SF-003 iPSC line may be a useful resource for in vitro modeling of A-T.

Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells.

Biallelic mutations in ATM result in the neurodegenerative syndrome Ataxia-Telangiectasia, while ATM haploinsufficiency increases the risk of cancer and other diseases. Previous studies revealed low reprogramming efficiency from A-T and carrier fibroblasts, a barrier to iPS cell-based modeling and regeneration. Here, we tested the feasibility of employing circulating erythroid cells, a compartment no or minimally affected in A-T, for the generation of A-T and carrier iPS cells. Our results indicate that episomal expression of Yamanaka factors plus BCL-xL in erythroid cells results in highly efficient iPS cell production in feeder-free, xeno-free conditions. Moreover, A-T iPS cells generated with this protocol maintain long-term replicative potential, stable karyotypes, re-elongated telomeres and capability to differentiate along the neural lineage in vitro and to form teratomas in vivo. Finally, we find that haploinsufficiency for ATM does not limit reprogramming from human erythroid cells or in vivo teratoma formation in the mouse.

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways.

In mammalian cells, chromatin poly(ADP-ribos)ylation (PARylation) at sites of DNA Double-Strand Breaks (DSBs) is mediated by two highly related enzymes, PARP1 and PARP2. However, enzyme-specific genetic interactions with other DSB repair factors remain largely undefined. In this context, it was previously shown that mice lacking PARP1 and H2AX, a histone variant that promotes DSB repair throughout the cell cycle, or the core nonhomologous end-joining (NHEJ) factor Ku80 are not viable, while mice lacking PARP1 and the noncore NHEJ factor DNA-PKcs are severely growth retarded and markedly lymphoma-prone. Here, we have examined the requirement for PARP2 in these backgrounds. We find that, like PARP1, PARP2 is essential for viability in mice lacking H2AX. Moreover, treatment of H2AX-deficient primary fibroblasts or B lymphocytes with PARP inhibitors leads to activation of the G2/M checkpoint and accumulation of chromatid-type breaks in a lineage- and gene-dose dependent manner. In marked contrast to PARP1, loss of PARP2 does not result in additional phenotypes in growth, development or tumorigenesis in mice lacking either Ku80 or DNA-PKcs. Altogether these findings highlight specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells.

A glimpse towards the vestigiality and fate of human vermiform appendix-a histomorphometric study.

INTRODUCTION: The vermiform appendix in human is considered to be a vestigial organ by most of the authors. Absence of appendix is already reported in Indian population. Whether the human appendix is performing any function is debatable but when present it can create trouble. So if there is no appendix we can escape the ill-effects of the organ. With this hope the study has been done to see whether the appendix is really going to be rudimentary or absent or not. Marerials and Methods: Length, external diameter, number of lymphoid follicles, maximum diameter of the follicle or submucous coat, thickening of the muscle coat and seromucosal thickening of freshly removed appendix from human cadavers were seen. After fixation in 10% formal saline tissues were stained with haematoxylin-eosin stain and photographs were taken. The results had been tabulated and statistically correlated. RESULT: The parameters like number of lymphoid follicles, length and diameter all are changed as per the age advancement which is strictly indicating some functional activities of the organ which is against the idea of vestigiality of the appendix. CONCLUSION: Human appendix cannot be called a vestigial organ unless the functional inactivity is proved. Lymphoid changes which occur after birth to provide the gut immunity is needed to be proved by further studies. There might be incidental absence or rudimentary appendix in human body, but that does not indicate that we would not have any appendix in future.

Targeting exosomes from preadipocytes inhibits preadipocyte to cancer stem cell signaling in early-stage breast cancer.

The tumor microenvironment plays a critical role in regulating breast tumor progression. Signaling between preadipocytes and breast cancer cells has been found to promote breast tumor formation and metastasis. Exosomes secreted from preadipocytes are important components of the cancer stem cell niche. Mouse preadipocytes (3T3L1) are treated with the natural antitumor compound shikonin (SK) and exosomes derived from mouse preadipocytes are co-cultured with MCF10DCIS cells. We examine how preadipocyte-derived exosomes can regulate early-stage breast cancer via regulating stem cell renewal, cell migration, and tumor formation. We identify a critical miR-140/SOX2/SOX9 axis that regulates differentiation, stemness, and migration in the tumor microenvironment. Next, we find that the natural antitumor compound SK can inhibit preadipocyte signaling inhibiting nearby ductal carcinoma in situ (DCIS) cells. Through co-culture experiments, we find that SK-treated preadipocytes secrete exosomes with high levels of miR-140, which can impact nearby DCIS cells through targeting SOX9 signaling. Finally, we find that preadipocyte-derived exosomes promote tumorigenesis in vivo, providing strong support for the importance of exosomal signaling in the tumor microenvironment. Our data also show that targeting the tumor microenvironment may assist in blocking tumor progression.

Evaluation of proximal femoral geometry in plain anterior-posterior radiograph in eastern-Indian population.

BACKGROUND: The morphologic features of the proximal femur are used in preoperative planning prior to total hip arthroplasty. The standard commercially available marketed prostheses sometimes may not be the best fit to all subjects because of the large anatomic variation among different population. Orthopaedic surgeons always stress the need for a proper implant-patient match in hip joint replacements to avoid post-operative complication of mismatch which may affect the ultimate outcome of the operation. AIM: The present study was undertaken to measure the important parameters of upper end of femur in elderly Eastern Indian population which will help the prosthetist to manufacture ideal implant for the local population. This will also help the orthopaedic surgeons while positioning the implants during total hip replacement (THR) procedure in this population. MATERIALS AND METHODS: Measurements were made on both sides, left and right from anterior-posterior radiograph of 102 subject (>50yrs, 42 male and 60 females) using AGFA software. Three parameters femoral head diameter (FHD), neck-shaft angle (NSA) and horizontal off-set (HO) were measured. RESULTS: SPSS software used for data analysis. Gender- wise no significant differences were found in NSA and FHD, but HO was significantly lower in female than that of male (p<.05).The values on both sides didn't differ significantly. CONCLUSION: Improved knowledge of the morphology of the proximal femora will assist the surgeon in restoring the geometry of the proximal femur during total hip arthroplasty and the data could be used as a guideline to design a more suitable implant for Eastern Indian population.

Morphometric study of left coronary artery trunk in adult human cadavers: a study on the eastern region population.

INTRODUCTION: The left coronary artery shows a wide range of morphological variations which has great clinical importance. Difficulties may occur during performance of diagnostic procedures, especially in patients who undergo evaluation of percutaneous coronary interventions or during coronary artery surgeries or prosthetic valve replacements. Even, it has been found that short length of main left coronary artery was one of the congenital factors which predisposed to the development of coronary artery disease. The aim of this work was to determine the variations in the origin, length and divisions of the left coronary artery trunk in the eastern region population of India. MATERIALS AND METHODS: The present study was carried out on 100 heart samples which were collected from a mixed race population group from West Bengal, India, after preserving them in 10% formalin solution. While carefully maintaining all standard precautions, scientifically well-planned cadaveric dissections were done and variations were noted. RESULTS: It was found that in all specimens, left coronary artery arose from single ostia at the left posterior aortic sinus. In about 65% cases, ostia was below or at the sinotubular junction (STJ) and in a significant number (35%) of cases, it is above the level of STJ. The mean length of the left coronary artery trunk was found to be 11.42 ± 4.98 mm. LMCA were bifurcated in 56% cases, they were trifurcated in 40% cases and they were tetrafurcated in 2% cases. The results were compared with those of other studies, which showed considerable variations. CONCLUSION: Thus, this morphometric study done on left coronary artery trunk in the eastern Indian population will be helpful for interventional cardiologists and radiologists for avoiding inadvertent vascular trauma during diagnostic and therapeutic procedures.

Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21.

Despite recent advancement in medicine, nearly 50% of patients with colorectal cancer show recurrence of the disease. Although the reasons for the high relapse are not fully understood, the presence of chemo- and radiotherapy-resistant cancer stem/stem-like cells, where many oncomirs like microRNA-21 (miR-21) are upregulated, could be one of the underlying causes. miR-21 regulates the processes of invasion and metastasis by downregulating multiple tumor/metastatic suppressor genes including PTEN (phosphatase and tensin homolog). Tumor suppressor protein PTEN controls self-renewal of stem cells. Indeed, our current data demonstrate a marked downregulation of PTEN in SCID mice xenografts of miR-21 over-expressing colon cancer HCT116 cells. Colonospheres that are highly enriched in cancer stem/stem like cells reveal increased miR-21 expression and decreased PTEN. Difluorinated curcumin (CDF), a novel analog of the dietary ingredient curcumin, which has been shown to inhibit the growth of 5-Flurouracil + Oxaliplatin resistant colon cancer cells, downregulated miR-21 in chemo-resistant colon cancer HCT116 and HT-29 cells and restored PTEN levels with subsequent reduction in Akt phosphorylation. Similar results were also observed in metastatic colon cancer SW620 cells. Since PTEN-Akt confers drug resistance to different malignancies including colorectal cancer, our observation of normalization of miR-21-PTEN-Akt pathway by CDF suggests that the compound could be a potential therapeutic agent for chemotherapy-resistant colorectal cancer.

Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF.

BACKGROUND: Colorectal Cancer (CRC) is one of the leading causes of death worldwide. Numerous cellular events, including deregulated expression of microRNAs (miRNAs), specifically the family of miR-34 consisting of miR-34a, b and c, is known to regulate the processes of growth and metastasis. METHODS: We evaluated the expression of miR-34 in formalin-fixed paraffin-embedded (FFPE) human colon cancer tissue specimens compared to normal colonic mucosa. Moreover, we also assessed the expression of miR-34 in colon cancer cell lines treated with our newly developed synthetic analogue of curcumin referred as difluorinated curcumin (CDF) compared to well known inhibitor of methyl transferase. RESULTS: We found that the expression of miR-34a and miR-34c was down-regulated in colon cancer specimens compared to normal colonic mucosa and the loss of expression was also consistent with data from colon cancer cell lines. This down-regulation was attributed to promoter hypermethylation, because we found that the treatment of colon cancer cells with 5-aza-2´-deoxycytidine, a methyltransferase inhibitor, markedly induced the levels of miR-34a and miR-34c expression. Likewise, CDF was very effective in the re-expression of miR-34a and miR-34c, which was consistent with inhibition of cell growth of both chemo-sensitive and chemo-resistant colon cancer cells. The re-expression of miR-34 led to a marked reduction in the expression of its target gene, Notch-1. CONCLUSION: The loss of expression of miR-34 in colon cancer is in part due to promoter hypermethylation of miR-34, which can be re-expressed with our novel agent CDF, suggesting that CDF could be a novel demethylating agent for restoring the expression of miR-34 family, and thus CDF could become a newer therapeutic agent for the treatment of colon cancer.

Two rare anatomical variations of external jugular vein: an embryological overview / Dos raras variaciones anatómicas de la vena yugular externa: una visión embriológica

Human anatomy is an ocean of unending variations and its mysteries are being unravelled since ages. Knowledge of variations in the superficial veins of head and neck is essential to carry out successful surgical procedures. During routine dissection of head and neck of two middle aged male cadavers, in the Department of Anatomy, Calcutta National Medical College, Kolkata, India, we came out with some interesting venous architecture. The retromandibular vein on the left side of both the cadavers was found to be undivided and joined with the facial vein in the neck at an acute angle to form a common venous trunk at variable distances from the angle of the mandible. That trunk ultimately drained into the left subclavian vein. This might be the result of disappearance of the cephalic part of the external jugular vein and formation of an additional communication between common facial vein and the external jugular vein in foetal life. In one case, we also came across an extra transverse communication between that common trunk and the internal jugular vein. A detail of those cases with embryological explanation is attempted...

La anatomía humana tiene un sin fin de variaciones y sus misterios se han develado desde el inicio de los tiempos. El conocimiento de las variaciones anatómicas de las venas superficiales de la cabeza y del cuello es fundamental para llevar a cabo con éxito los procedimientos quirúrgicos. Durante una disección de rutina de cabeza y cuello encontramos una arquitectura venosa interesante en dos cadáveres de hombres de mediana edad en el Departamento de Anatomía de la Facultad de Medicina Nacional Calcuta, Calcuta, India. En el lado izquierdo del cuello de ambos cadáveres, la vena retromandibular no se encontraba dividida, y se unía a la vena facial en un ángulo agudo, para formar un tronco venoso común a una distancia variable desde el ángulo de la mandíbula. Ese tronco finalmente drenaba en la vena subclavia izquierda. Esto podría ser el resultado de la desaparición de la parte cefálica de la vena yugular externa y la formación de una comunicación adicional entre la vena facial común y la vena yugular externa en la vida fetal. En un caso, también se encontró con una comunicación adicional transversal entre ese tronco común y la vena yugular interna. Se realiza una descripción en detalle de los casos junto a una explicación embriológica...