ARID1A loss correlates with high-grade endometrial carcinomas



BAF250a (ARID1A) loss is a frequent event in high-grade endometrial cancers. It has been proposed that ARID1A is a driver gene, with ARID1A mutations occurring secondary to deregulated mismatch repair mechanism in gastric cancers, representing an alternative oncogenic pathway to p53 alteration. The prognostic significance of ARID1A loss is controversial. In this study, we investigated the frequency of BAF250a immunohistochemical loss in a cohort of high-grade endometrial cancers (n=190) and correlated it with mismatch repair (hMLH1, hMSH2, hMSH6, and hPMS2) and p53 protein expression. The 190 cases consisted of 82 high-grade endometrioid, 88 serous, 10 clear cell, and 10 mixed (carcinosarcomas and mixed histology). There was BAF250a loss in 55/190 (29%) cancers, most commonly in high-grade endometrioid carcinomas (46 vs 9% in serous carcinomas, P<0.0001). Loss of any mismatch repair proteins was observed in 63/190 (33%) cancers, most commonly in high-grade endometrioid carcinomas (57 vs 10% in serous carcinomas, P<0.0001). Aberrant p53 expression was found in 86/190 (45%) cancers, more commonly in serous carcinomas (77 vs 18% in high-grade endometrioid carcinomas, P<0.0001). BAF250a loss was associated with mismatch repair loss (P<0.0001) and normal p53 expression (P<0.0001). These associations were maintained in the subset analysis within the high-grade endometrioid (P=0.026 and P=0.0083, respectively) and serous carcinoma cases (P=0.0031 and P<0.0001, respectively). Survival analysis revealed a superior progression-free survival (P=0.017) for patients with BAF250a loss within the entire cohort but not within the high-grade endometrioid and serous subtypes. Additionally, data from The Cancer Genome Atlas were extracted to correlate mutations in ARID1A, TP53, and MMR genes; we found that ARID1A mutations were negatively associated with TP53 mutations but were unrelated to mismatch repair gene mutations. In conclusion, BAF250a loss is more common in high-grade endometrioid carcinomas than in other high-grade endometrial cancers and is associated with mismatch repair deficiency and normal p53 expression.

نمرات نهایی هماتولوژی و انتقال خون ترم 3 اتاق عمل پیوسته

کوه نژاد 18

راجی 17.75

طاعت 17

نوروزی 15.75

ابراهیمی 12.5

اسکندری 10.75

اشکانی 13.75

اکبری ندا 10

امین نژاد 13.5

بابایی روشن 12.75

بخشی پور 13

پوراختیار 12.75

پیشه گر 12

جهانی پور 12.25

حسن زاده 14.75

رضایی انور 11

روشی 13

سحرخیز 13.75

سعادت پور 15

شاهدی 12.75

شعبانی 15.25

شفاعی 13.25

عبدی 12.75

کارگرپور 15.5

کاوش 13.5

محمدی 15

ملک پور 15.5

مومنی زاده 11.25

میریگانه 16

نوبخت 15

نورعلی زاده 13.75

نیلاش 14.25

یوسفی 12.75

پادنگ چیان 14.75

اکبری شایان 13.5

ارتقاء 12.25

شرفی نژاد 10

علی دوست 11.75


Origins of aberrant DNA methylation in acute myeloid leukemia


Aberrant DNA methylation patterns are a characteristic feature of cancer including myeloid malignancies such as acute myeloid leukemia (AML). The mechanisms behind aberrant DNA methylation have long remained obscure. New genome-wide studies have elucidated the genome and epigenome of solid tumors and AML. Molecular subtypes of AML were found to exhibit highly distinct DNA methylation profiles. Clonal evolution patterns of AML were recently dissected and might shape epigenetic dysregulation. Also, recurrent mutations in epigenetic modifying enzymes were identified in AML and linked to distinct DNA methylation signatures. The genetic background, thus, takes center stage as a driver of epigenetic dysregulation in AML. First mechanistic insights into the dysregulation of DNA methylation by recurrent mutations have already been gained. Other studies suggest that epigenomic plasticity and aging-associated changes in DNA methylation also contribute extensively to aberrant DNA methylation in cancer. Epigenetic dysregulation, therefore, seems to also occur independently of the genetic background. Furthermore, global changes in chromatin conformation and nuclear organization have also been proposed as potential contributors to aberrant DNA methylation
.

نمرات نهایی ترمینولوژی پزشکی ترم 2 علوم آزمایشگاهی ناپیوسته

نمرات از 20 می باشد:

حسنی 18.75

درقش 14.5

رجبی 17.25

شریفی 17.75

شعبانیان 15.5

صادقی 14.5

غلامی 16.75

فلاح شجاعی 11

قادری 14.5

قدیمی 14.75

مرات 14

موسوی 15.25

نژاد مقدم 10

نوروزی 17.5

یعقوب زاده  18.25

تحریری 14

عطایی 10


کنگره ملی برنامه جامع کنترل سرطان


مشكل استفاده باليني از سلول‌هاي بنيادي جنيني


يكي از مشكلات اساسي بر سر راه استفاده باليني از سلول‌هاي بنيادي جنيني وجود سلول‌هايي است كه به طور كامل تمايز پيدا نكرده‌اند. سلول‌هاي بنيادي جنيني با استفاده از عوامل رشد قادرند به انواع سلول‌هاي تشكيل دهنده بافت‌ها تمايز يافته و در ترميم بافت‌هاي آسيب ديده مورد استفاده قرار گيرند. با اين حال درصورتي كه سلول‌ها به طور كامل تمايز پيدا نكنند به دليل خاصيت چند قوه بودن یا Multipotent  ممكن است موجب ايجاد تراتوما كه در واقع نوعي سرطان است، گردد. به همين دليل جداسازي سلول‌هاي تمايز نيافته از بين سلول‌هاي تمايز يافته مي‌تواند اين عارضه را به طور موثري كاهش دهد. محققان دانشگاه استنفورد موفق شدند پروتئيني را شناسايي نمايند كه به طور اختصاصي بر سطح سلول‌هاي تمايز نيافته بيان مي‌شود. استفاده از آنتي‌بادي عليه اين پروتئين مي‌تواند سلول‌هاي پيوند شده را عاري از سلول‌هاي تمايز نيافته نمايد. با اين حال تا استفاده باليني از اين آنتي‌بادي راه طولاني در پيش است و در حال حاضر در اغلب مراكز از جمله پژوهشگاه رويان تنها از سلول‌هاي بنيادي بزرگسالان براي درمان بيماران استفاده مي‌كنند كه عارضه ايجاد تراتوما را ندارند.

نمرات نهایی هماتولوژی 2 ترم 2 علوم آزمایشگاهی ناپیوسته


نمرات از 20 می باشد:

حسنی 17.75

درقش 15.25

رجبی 15.25

شریفی 17.25

شعبانیان 15.5

صادقی 16.25

غلامی 15.5

فلاح شجاعی 16.5

قادری 15.5

قدیمی 14.5

مرات 14.25

موسوی 14.25

نژاد مقدم 13.75

نوروزی 17

یعقوب زاده 17.5

Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway


The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8+ cells, these patients also had increased fractions of CD8+CD45RO-CD62L+ plus CD8+CD45RO+CD62L+ subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing.

EVI1 expression in childhood ALL is not restricted to MLL and BCR/ABL rearrangements


EVI1 is a transcriptional regulator with an important function in haematopoiesis and self-renewal.Aberrant overexpression of EVI1 has been firmly established as one of the most adverse prognostic markers in acute myeloid leukaemia (AML), implying that EVI1 is one of the most aggressive oncogenes in AML.

Importantly, a recent report in Leukemia from Konantz et al.suggests that EVI1 might also have a role in paediatric acute lymphoblastic leukaemia (ALL), where high expression confers apoptosis resistance, and possibly also an adverse prognosis. Rearrangements of the 3q26 region, which encompasses the MECOM (MDS–EVI1 complex) gene that encodes EVI1 transcripts and that are commonly associated with EVI1 overexpression in adult AML, rarely occur in childhood ALL or AML. However, when EVI1 is expressed in childhood AML it seems to be predominate in MLL-rearranged cases, which may then confer an adverse prognosis, as illustrated by the correlation with the t(6;11) subtype,and with complex karyotype cases. However, in general high EVI1 expression is not seen in AML with good prognosis cytogenetics such as core-binding factor-rearranged AML with t(8;21) or inv(16). In addition, in chronic myeloid leukaemia, the BCR–ABL fusion tyrosine kinase sustains EVI1 expression.


نمرات نهایی هماتولوژی 1 ترم 3 علوم آزمایشگاهی پیوسته

نمرات از 20 می باشد:


داوطلب 16.75

رمضانپور 16.5

گلشن 15

قاسمیه 14.5

ابراهیمی 14.75

تقوی 12.25

کشاورز 13.25

ولی زاده 12.5

داودی مقدم 13.25

وفادار 12.75

صفری 10

منفردی 14.5

قدرجانی 11

خوشحال 14.5

مولودی 12.75

فوائیدی 10

مهدی نژاد 13.25

علیزاده 13

جعفرپور 13.5

خالص زاده 13

آزادگان 13.25

علیپور 11.25

بحیرایی 12.75

امام جمعه 12.25

قربانی 11.75

کیمیاگر 10

صالحی 12.25

جلالی زاده 12.75

ساکتی 14.25

نظری 10.75

بابا احمدی 10.5

ارجمندی 10.5

منتظر نظرات و پیشنهادات شما هستیم موفق باشید

Self-renewal as a therapeutic target in human colorectal cancer


Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1 inhibits the ability of colorectal CICs to self-renew, resulting in the abrogation of their tumorigenic potential. Treatment of primary colorectal cancer xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss with long-term and irreversible impairment of tumor growth. Targeting the BMI-1–related self-renewal machinery provides the basis for a new therapeutic approach in the treatment of colorectal cancer.

واكسن اچ.آی.وی با موفقيت بر روی ميمون ها آزمايش شد

محققان موسسه واكسن و ژن درماني دانشگاه علوم پزشكي اورگان آمريكا مي گويند: واكسن اچ آي وي كه بر روي ميمون ها آزمايش شده، حركت اين ويروس را متوقف كرده است.

محققان موسسه واكسن و ژن درماني دانشگاه علوم پزشكي اورگان آمريكا مي گويند: واكسن اچ آي وي كه بر روي ميمون ها آزمايش شده، حركت اين ويروس را متوقف كرده است.

واكسن جدید طراحي شده براي مقابله با بيماري (SIV) كه در ميمون معادل بيماري ايدز(HIV) است، با موفقيت ويروس را از بدن حيوانات آلوده پاكسازي كرده و راه را براي آزمايش واكسن (HIV) بر روي انسان هموار ساخته است.

در اين مطالعه از مجموع ۱۶ ميمون در معرض ويروس، كه به آن ها واكسن تزريق شده بود، ۹ ميمون توانستند بدن خود را از اين ويروس پاك كنند.

محققين حركت ويروس (SIVmac۲۳۹) را كه ۱۰۰ برابر بيشتر از ويروس(HIV) مرگبار است، بررسي كردند. آن ها نخست به ميمون ها واكسن تزريق كرده و سپس آن ها را در معرض ويروس (SIV) قرار دادند.

نتايج به دست آمده نشان مي دهد اين ويروس در بيش از نيمي از ميمون هاي آلوده كه واكسن تزريق كرده اند، گسترش نمي يابند. اين ميمون ها بدون تزريق واكسن در مدت دو سال پس از آلودگي به ويروس، جان خود را از دست مي دهند.

واكسن مورد نظر كه نسخه اصلاح شده ويروس سيتومگالويروس(CMV) است به خانواده ويروس تبخال تعلق دارد. اين ويروس در سراسر بدن ميمون منتشر شده و سيستم ايمني بدن را براي مبارزه با ويروس (SIV) تقويت مي كند.

محققان اميدوارند بتوانند از روش مشابه براي آزمايش واكسن ايدز بر روي انسان استفاده كنند.

تا سال ۲۰۱۳ بيش از ۳۵ ميليون نفر در سراسر دنيا به ويروس HIV مبتلا شده اند و تا سال ۲۰۰۹ نيز اين ويروس سبب مرگ بيش از ۳۰ ميليون نفر در سراسر دنيا شده است.

چه کسانی نباید واکسن آنفلوانزا بزنند؟

اولویت  و اندیکاسیون تزریق واکسن آنفوانزا به این ترتیب است: بیماران دیالیزی و پیوند کلیه، بیماران تالاسمی ماژور، بیماران کبدی شامل: سیروز و پیوند کبد، بیماران سرطانی که تحت شیمی درمانی یا رادیوتراپی قرار دارند و در آخر پرسنل بهداشتی درمانی.

تزریق واکسن در کسانی که سابقه واکنش آلرژیک به مواد موجود در واکسن آنفلوانزا را دارند مانند تخم مرغ، فرمالدهید، جنتامایسین، کسانی که در زمان مراجعه برای تزریق واکسن تب یا عفونت حاد داشته باشند، کسانی که سابقه ابتلا به سندرم گیلن باره را داشته باشند و شیر خواران زیر 6 ماه ممنوع است.

واکسن های آنفلوانزا در تمام مراحل بارداری قابلیت مصرف دارند. اطلاعات عمده تری در مورد بی خطری این دارو در سه ماهه دوم و سوم نسبت به سه ماهه اول بارداری در دسترس می باشد. همچنین واکسن آنفلوانزا را می توان در دوران شیردهی تجویز کرد.
 واکسن آنفلوانزا باید در دوزی که پزشک تجویز کرده به صورت داخل عضلانی یا زیر جلدی عمیق تزریق شود.

77 نوع ماده سرطان زا، هدیه ظروف یکبار مصرف

ظروف یکبار مصرف پلیمری و کیسه‌های پلاستیکی در صورت تماس با مایعات و مواد غذایی بالای 40 درجه، ماده‌ای شیمیایی به نام استایرن از خود خارج می‌کنند که شدیدا کارسینوژن بوده و گهگاه منجر به تندی غذا می‌شود . این ظروف بیش از 77 نوع ماده سرطان‌زا را به‌همراه دارند. پس هدیه ظروف یکبار مصرف را بخوبی بشناسیم

نمرات میان ترم علوم پیوسته ترم 3

نمرات از 7 می باشد:

رمضانپور 6.5

گلشن 6.25

قاسمیه 6.25

داوطلب 6.25

ابراهیمی 6.25

تقوی 5

کشاورز 4.25

ولی زاده 4

داودی مقدم 5.75

وفادار 5

صفری 3.5

منفردی 5.25

قدرجانی 5

خوشحال 6

مولودی 4.75

فوائیدی 4.75

مهدی نژاد 4.24

علیزاده 5.5

جعفرپور 6

خالص زاده 4.5

آزادگان 4.75

علیپور 4.75

بحیرایی 4.75

امام جمعه 4.75

قربانی 4

کیمیاگر 4.5

صالحی 4.75

جلالی زاده 4.75

ساکتی 5.5

نظری 3.5

بابا احمدی 3

ارجمندی 3

منتظر نظرات و پیشنهادات شما هستیم موفق باشید

Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early

Background:

Many micro-RNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue and previous reports have suggested the possibility of serum miRNAs as complementary tumour markers. The aim of the study was to investigate serum miRNAs and pepsinogen levels in individuals at high risk for gastric cancer both before and after H. pylori eradication.

Methods:

Patients with recent history of endoscopic resection for early gastric cancer and the sex- and age-matched controls were enrolled. Serum was collected from subjects before or after eradication and total RNA was extracted to analyse serum levels of 24 miRNAs. Serum pepsinogen (PG) I and II levels were measured using enzyme-linked immunosorbent assay kits.

Results:

Using miR-16 as an endogenous control, the relative levels of miR-106 and let-7d before and after H. pylori eradication and miR-21 after eradication were significantly higher in the high-risk group than in the controls. H. pylori eradication significantly decreased miR-106b levels and increased let-7d only in the control group. After eradication, the combination MiR-106b with miR-21 was superior to serum pepsinogen and the most valuable biomarker for the differentiating high-risk group from controls.

Conclusion:

Serum miR-106b and miR-21 may provide a novel and stable marker of increased risk for early gastric cancer after H. pylori eradication.

A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma

Background:

Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured.

Methods:

Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55mgm–2) with doxorubicin reduced to 25mgm–2 or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD.

Results:

Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55mgm–2, so 45mgm–2 was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD.

Conclusion:

Escalated ABVD incorporating doxorubicin at 45mgm–2 in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies.

Mutation landscape in melanoma patients clinical implications of heterogeneity of BRAF mutations


Background:

The detection of V600E BRAF mutations has fundamental clinical consequences as the treatment option with BRAF inhibitors such as vemurafenib or dabrafenib yields response rates of ~48%. Heterogeneity with respect to BRAF mutation in different metastases has been described in single cases. As this has important implications for the determination of BRAF status and treatment of patients, it is essential to acquire more data.

Methods:

A total of 300 tumour samples from 187 melanoma patients were analysed for BRAF mutations by pyrosequencing. Equivocal results were confirmed by capillary sequencing. Clinical data with respect to melanoma type, tumour site and survival were summarised for 53 patients with multiple analysed tumour samples (2–13 per patient).

Results:

BRAF mutations were found in 84 patients (44.9%) and 144 tumour samples (48%) with BRAF mutations in 45.5% of primary tumours and 51.3% of metastases, respectively. In 10 out of 53 patients (18.9%) where multiple samples were analysed results were discordant with respect to mutation findings with wild-type and mutated tumours in the same patient. Mutations did not appear more frequently over the course of disease nor was its occurrence associated with a specific localisation of metastases.

Conclusion:

As heterogeneity with respect to BRAF mutation status is detected in melanoma patients, subsequent testing of initially wild-type patients can yield different results and thus make BRAF inhibitor therapy accessible. The role of heterogeneity in testing and for clinical response to therapy with a BRAF inhibitor needs to be further investigated.

The effect of metformin on apoptosis in a breast cancer presurgical trial

Background: 

Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial.

Methods:

Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery.

Results:

Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2–12; placebo arm: +2%, IQR: 0–8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman’s r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2–14 vs +2%, IQR: 0–7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0–6, vs +5%, IQR: 0–15 on placebo, P-interaction=0.1).

Conclusion: 

Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status

.

Prognostic/predictive value of 207 serum factors in colorectal cancer

Background:

The prognostic and predictive value of multiple serum biomarkers was evaluated using samples from a randomised phase III study (HORIZON II) investigating chemotherapy with or without cediranib in metastatic colorectal cancer (mCRC).

Methods:

Baseline levels of 207 protein markers were measured in serum samples from 582 HORIZON II (FOLFOX/XELOX plus cediranib 20mg (n=330) or placebo (n=252)) patients. Median baseline values of each biomarker were used to categorise patients as high or low. Markers were then assessed for their association with efficacy, defined by progression-free survival (PFS) and overall survival (OS). A generalised boosted regression model identified markers of particular interest.

Results:

Correlation of protein levels with PFS and OS suggested that multiple factors had a prognostic value, independent of treatment arm, including IL-6, IL-8, C-reactive protein (CRP), ICAM-1 and carcinoembryonic antigen (CEA). Among the angiogenesis regulators, low levels of vascular endothelial growth factor (VEGF), VEGF-D, VEGFR-1, VEGFR-3, NRP1 and Tie-2 correlated with better outcome.

Conclusion: 

This large data set generated using serum samples from mCRC patients treated with chemotherapy and VEGF inhibitors, defines baseline characteristics for 207 serum proteins. Multiple prognostic factors were identified that could be disease related or predict which patients derive most benefit from 5-fluorouracil (5-FU)-based chemotherapy, meriting further exploration in prospective studies

.

Interleukin-21 (IL-21) is a common γ-chain cytokine produced by T helper and natural killer T (NKT) cells. It has been shown to regulate the response of various lymphocyte subsets including NK, NKT, T and B cells. Owing to its potent anti-tumor function in preclinical studies and its ability to induce cytotoxicity and interferon-γ (IFN-γ) production in NK and CD8 T cells, recombinant IL-21 (rIL-21) was fast-tracked into early-phase clinical trials of patients with various malignancies. In a phase 2a trial of patients with metastatic melanoma, we analyzed the frequency and function of NKT cells in patients receiving rIL-21. NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. Unlike our observations in NK and CD8 T cells, rIL-21 appeared to reduce IFN-γand TNF production by NKT cells, whereas it enhanced IL-4 production. It also modulated the expression of cell surface markers, specifically on CD4NKT cells. In addition, an increase in CD3+CD56+ NKT-like cells was observed over the course of rIL-21 administration. These results highlight that IL-21 is a potent regulator of NKT cell function in vivo

Protein S levels and the risk of venous thrombosis


In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n = 5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free and total protein S deficiency was not associated with venous thrombosis: free protein S < 53 U/dL, odds ratio [OR] 0.82 (95% confidence interval [CI], 0.56-1.21) and total protein S < 68 U/dL, OR 0.90 (95% CI, 0.62-1.31). When lower cutoff values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in 5 patients and 5 controls reinforcing the observation that inherited protein S deficiency is rare in the general population.

Autologous Transplantation as Consolidation for Aggressive Non-Hodgkin's Lymphoma


Background

The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era

Methods

We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival.

Results

Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P=0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P=0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P=0.04 for interaction) and overall survival (P=0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group.

Conclusions

Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation. (Funded by the National Cancer Institute, Department of Health and Human Services, and others; SWOG-9704 ClinicalTrials.gov number, NCT00004031.)

.

tumour immunotherapy for the treatment of cutaneous melanoma


Immunotherapy is associated with durable clinical benefit in patients with melanoma. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA. To achieve this goal, the Society for Immunotherapy of Cancer sponsored a panel of melanoma experts—including physicians, nurses, and patient advocates—to develop a consensus for the clinical application of tumour immunotherapy for patients with melanoma. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development. A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel. This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. From the peer-reviewed literature the consensus panel identified a role for interferon-α2b, pegylated-interferon-α2b, interleukin-2 (IL-2) and ipilimumab in the clinical management of melanoma. Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted.

The Cancer Genome Atlas Pan-Cancer analysis project

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profileCancer can take hundreds of different forms depending on the location, cell of origin and spectrum of genomic alterations that promote oncogenesis and affect therapeutic response. Although many genomic events with direct phenotypic impact have been identified, much of the complex molecular landscape remains incompletely charted for most cancer lineages.

برندگان جایزه نوبل پزشکی 2013 معرفی شدند/ حل معمای انتقال سلولی


جایزه نوبل فیزیولوژی یا پزشکی سال 2013 به جیمز ایی روتمان، رند دبلیو شکمان و توماس سی شدهوف برای کشف یک سیستم مهم در سلولهای بدن اهدا شد.

این جایزه به جیمز ایی روتمان آمریکایی استاد علوم بیوپزشکی در دانشگاه یل و رئیس دپارتمان بیولوژی سلولی دانشکده پزشکی دانشگاه یل است.

توماس شدهوف بیوشیمیست آلمانی است که برای تحقیقاتش در انتقال سیناپسی شناخته می شود. در حقیقت تلاشهای وی بنیاد درک کنونی علمی را از انتقال دهنده عصبی " vesicle-mediated" فراهم کرده است.

رندی وین شکمان آمریکایی زیست شناس سلولی دانشگاه کالیفرنیا و سردبیر سابق مجله مقالات آکادمی ملی علوم است.

در 27 نوامبر 1895 آلفرد نوبل آخرین وصیت خود را امضا کرد و بیشتر دارایی خود را به جایزه‌ای اختصاص داد تا همه ساله بدون توجه به ملیتی خاص، به افراد شایسته اهدا شود. براساس وصیت نوبل، بخشی از این جوایز به فردی اهدا می شود که مهمترین کشف را در حوزه فیزیولوژی یا پزشکی کرده است.

جایزه نوبل فیزیولوژی و پزشکی یکی از جایزه‌های نوبل است که هر سال از سوی انستیتوی کارولینسکا اعطا می‌شود. جایزه امسال توسط "گوران کی. هانسون" دبیر کمیته فیزیولوژی یا پزشکی بنیاد نوبل اعلام شد.

تحقیق این 3 دانشمند به اینکه سلول چگونه سیستم انتقال خود را سازمان دهی می کند، پاسخ داده است.

تحقیقات برندگان نوبل پزشکی امسال که هر سه در دانشگاه های آمریکایی فعالیت می کنند، به توضیح فرآیندهای متنوعی چون آزاد شدن انسولین در خون، ارتباط بین سلولهای عصبی و نحوه آلوده شدن سلولها توسط ویروسها کمک می کند.

آنها به شیوه عملکرد وزیکولها که شبیه یک دسته کشتی که کالاهای خود را به یک نقطه مشخص می رسانند، پی برده اند. این کشف برای درک شیوه برقراری ارتباط مغز و آزاد کردن هورمون ضروری است.

براساس اعلام کمیته نوبل پزشکی این تحقیقات تأثیر مهمی بر درک ما از چگونگی انتقال محموله با زمان بندی و تعیین محل دقیق به خارج از سلول دارد، بدون این سازمان دقیق و فوق العاده سلول با آشفتگی و هرج و مرج رو به رو می شود

لیست اسامی ۷۳ قلم دارو و واکسن در دست تولید کشور

معاون تحقیقات و فناوری وزارت بهداشت فهرست اسامی ۷۳ قلم دارو و واکسنی که به تازگی مجری طرح آنها مشخص شده و در مرحله صنعتی شدن قرار گرفته‌اند و همچنین داروهایی که مجوز تولید گرفته‌اند را به همراه اسامی دانشگاه‌های فعال اعلام کرد.


داروهایی که تولید صنعتی شده اند

13 دارو شامل:

Salmeterole, Antihemophilic factor VII, Riluzole, Trastuzumab, Letrozol, Botulinum toxin , Zoledronic acid, Etanercept, PEG-GCSF, لوپرولاید آهسته رهش،هورمون FSH، هورمون PTH،واکسن hib

داروهایی که دانش فنی را کسب نموده و نیاز به صنعتی شدن دارند

15 دارو شامل:

،Irinotecan, Warfarin, Cetrorelix, cytarabine, Bortezomib, Capecitabine, Vorinostat, Erlotinib, Gemcitabine, Imatinib, Sunitinib, Dcetaxel, Antihemophilic factor VIII, Fluticasone, Cetuximab

داروهایی که در مرحله کسب دانش فنی هستند

18دارو شامل:

Formoterol, Rituximab, Raloxifen, Infliximab, Granisetron, Oxaliplatin, TPA reteplase, TPA tenecteplase, Imipenem, Rivastigmine, Alprazolam, Paclitaxel, Cisatracurim, Carvedilol, Imiquimod, Zolpidem, Doxepin, Meropenem

داروهایی که تامین اعتبار شده اند تا تحقیق برای آنها آغاز شود

27دارو شامل:

Donepezil, Minoxidil, Montalukast, Ibandronate, Argireline, Salbutamol, Brimonidine, Valsartan, Tizanidine, Linezolid, Albumin, Zafirlukast, Adapalene, Cyclophosphamide, Chlorambucil, Acetylcysteine, Cromolin, Flourouracil, Prilocaine-F, Polyvinyl Alcohol, Epinephrine, Ferrous Glycine sulphate, Pimozide, Dorzolamide, Busulfan, Pramipexole،تزریقی آهسته رهش Naltrexone


اسامی داروها به تفکیک عقد قرارداد با دانشگاههای علوم پزشکی


ادامه نوشته

Pharmacological targeting of eIF4E in primary CLL lymphocytes


Eukaryotic translation initiation factor 4E (eIF4E) is a rate-limiting factor for cap-dependent protein synthesis regulated by the PI3K/AKT/mTOR signaling pathway as well as MNK1/2-mediated phosphorylation.1, 2 In addition to its cytoplasmic functions in translation, nuclear eIF4E aids in the cytoplasmic export of specific mRNAs.1, 3 eIF4E is overexpressed in many cancers and has been reported to have important roles in the development and progression of hematological malignancies in animal models.2 However, the role of eIF4E in drug resistance in primary human cancer cells is less well documented.4, 5, 6 In this study, we sought to assess the contribution of eIF4E to fludarabine (FLU) resistance in primary chronic lymphocytic leukemia (CLL) lymphocytes as this nucleoside analog is used as a first-line treatment for the disease.7 To this end, we used a panel of primary CLL samples from 26 affected patients (Supplementary Table). To interfere with eIF4E function, we used Ribavirin, a well-characterized antiviral drug that has also been shown to target eIF4E in a variety of systems, including patients with acute myeloid leukemia (AML).6, 8, 9 A clinically achievable concentration of Ribavirin (10μM), which was not cytotoxic to primary CLL lymphocytes in culture, significantly sensitized 76% of the samples tested to FLU with the sensitization index (R) ranging from 1.25 to eightfold (Figures 1a, P<0.001 and Supplementary Table). Sensitization was observed in 50% of the CD38-positive samples, 60% of the del17-positive samples, 50% of the del11-positive samples and samples from clinically resistant patients (Supplementary Table). Notably, the effect of Ribavirin was significantly associated with IgVH status, as revealed by the non-parametric Spearman Rank Order Correlation (r=−0.45, P=0.02); that is, better sensitization in high-risk U-IgVH samples, (Figure 1b).

برنامه کارورزی رشته علوم آزمایشگاهی ناپیوسته دانشکده پرستاری و مامایی-پیراپزشکی شرق گیلان -لنگرود


برنامه کارورزی رشته علوم آزمایشگاهی ناپیوسته دانشکده پرستاری و مامایی-پیراپزشکی شرق گیلان -لنگرود

نیمسال اول93-92

نام واحد:کارورزی در عرصه                                                   میزان واحد:12 واحد

روزهای کارورزی:شنبه لغایت پنج شنبه                                    ساعات کارورزی: 7:30 لغایت 13:30

 

گروه

گروهA

گروه B

گروه C

گروه D

اسامی دانشجویان/تاریخ و زمان کارورزی(شنبه لغایت سه شنبه)

1-پریسا حق جو

2- مجید آزادبر

3-پژمان محمدیان

4-مهناز شهبندی

1-مسعود بختیاری

2-سعیده حسینی

3-فرشید موسوی

4-وطن خواه

 5-متین دوست فاطمه

1-جواد سهرابی

2-عبدا... عزیززاده

3-امان ا... حکمی

4-متین اصغرنژاد

 

1-نسرین قنبری

2-نساء میراعلایی

3-الهام مرسلی

4-ربابه رضایی

5-مژگان نصیری

 

 

30/06/92 لغایت 5/07/92

 

  Work shop

06/07/92لغایت26/07/92

سازمان انتقال خون

آزمایش رفرانس

بیمارستان امینی

بیمارستان 22 آبان

27/07/92 لغایت 17/08/92

آزمایشگاه رفرانس

سازمان انتقال خون

بیمارستان 22 آبان

بیمارستان امینی

18/08/92 لغایت 08/09/92

بیمارستان پورسینا

بیمارستان الزهرا

سازمان انتقال خون

مرکز بهداشت رودسر

09/09/92 لغایت 29/09/92

بیمارستان الزهرا

بیمارستان ولایت

آزمایش رفرانس

سازمان انتقال خون

30/09/92 لغایت 20/10/92

بیمارستان حشمت

بیمارستان رازی

مرکز بهداشت رودسر

آزمایش رفرانس

21/10/92 لغایت 11/11/92

بیمارستان رازی

بیمارستان حشمت

بیمارستان امینی

مرکز بهداشت لنگرود

13/11/92

Final Exam

 

برنامه کارورزی رشته علوم آزمایشگاهی پیوسته در نیمسال اول93-92

برنامه کارورزی رشته علوم آزمایشگاهی پیوسته دانشکده پرستاری و مامایی-پیراپزشکی شرق گیلان -لنگرود

نیمسال اول93-92

نام واحد:کارورزی در عرصه                                                   میزان واحد:8 واحد

روزهای کارورزی:شنبه لغایت سه شنبه                               ساعات کارورزی: 7:30 لغایت 13:30

 

گروه

گروهA

گروه B

گروه C

گروه D

گروه E

اسامی دانشجویان/تاریخ و زمان کارورزی(شنبه لغایت سه شنبه)

1-محمد اشکانی

2-میلاد حشمتیان

3-مبین خوش بین

4-پوریا حنیفه پور

5-کسری هنرمند

1-غلامی

2-نگار ذاتی

3-محدثه پوررمضان

4-نادیا حیدری

1-زهره علیانفر

2-فرشته اکبری

3-سودابه باقری

4-شیوا مهدی زاده

5-ساناز مصافی

1-حمید جهان تیغ

2-فاطمه فتح آبادی

3-محمد پور عزت

4-حمید قمی

5-ریحانه اصغری

1-طاهره حجتی پور

2-شفیعی نیا

3-حبیب نصرا...زاده

4-مینا عاجلی

5-جانعلی زاده

30/06/92 لغایت 5/07/92

Work shop

06/07/92لغایت26/07/92

بیمارستان پورسینا

بیمارستان الزهرا

بیمارستان حشمت

مرکز بهداشت رودسر

مرکز بهداشت لنگرود

27/07/92 لغایت 17/08/92

بیمارستان الزهرا

بیمارستان پورسینا

بیمارستان رازی

مرکز بهداشت لنگرود

مرکز بهداشت رودسر

18/08/92 لغایت 08/09/92

بیمارستان حشمت

بیمارستان رازی

آزمایش رفرانس

بیمارستان امینی

بیمارستان 22 آبان

09/09/92 لغایت 29/09/92

بیمارستان رازی

بیمارستان حشمت

بیمارستان پورسینا

بیمارستان 22 آبان

بیمارستان امینی

30/09/92 لغایت 20/10/92

بیمارستان پورسینا

بیمارستان ولایت

بیمارستان الزهرا

بیمارستان امینی

بیمارستان 22 آبان

21/10/92 لغایت 11/11/92

آزمایش رفرانس

بیمارستان الزهرا

بیمارستان ولایت

مرکز بهداشت رودسر

مرکز بهداشت لنگرود

13/11/92

Final Exam