A Novel and Disease Specific Gene in Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 770-770 ◽  
Author(s):  
Anne Mette Buhl ◽  
Jesper Jurlander ◽  
Lone B. Pedersen ◽  
Par Josefsson ◽  
Christian H. Geisler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Gene Dosage ◽  
Specific Gene ◽  
Rt Pcr ◽  
Time To Treatment ◽  
Qrt Pcr ◽  
Poor Outcome ◽  
Disease Specific

Abstract One of the best predictors of poor outcome in CLL is the absence of somatic hypermutations in the Ig-genes of the leukemic cells. This prognostic dichotomy, between cases of mutated and unmutated CLL, enabled us to screen for a gene associated with poor outcome CLL using differential display RT-PCR. We identified a novel transcript from chromosome 12q22, which by RT-PCR and Northern blotting seemed to be selectively over-expressed in CLL patients with poor prognosis. No matching genes or ESTs were annotated in the region, but screening of a cDNA library from unmutated CLL patients resulted in cloning of 7 cDNAs, which probably derived from alternative splicing of a common transcript. The majority of the transcripts had no significant reading frames, but one splice variant may encode a protein of 121 amino acids. Despite very low primary sequence similarity, structure modelling revealed that the peptide potentially can fold into a structure remarkably similar to human IL-4. By RT-PCR the various transcripts were undetectable in a panel of normal tissues and cell lines. Using quantitative RT-PCR (QRT-PCR), we could however detect minute amounts of the mRNAs in normal B-cells; the level was similar or slightly higher in good prognosis patients and much higher in poor prognosis patients. The expression level of the two major mRNAs was 24–50 fold higher in patients with unmutated Ig-genes compared to patients with somatic hypermutation (p<0.0001), and 20–30 fold higher in ZAP-70 positive patients compared to ZAP-70 negative patients (p<0.0001). The median time to treatment for patients with overexpression of the mRNAs (n=26) was 11 months compared to 104 months for patients with normal expression (n=31) (p=0.0005). The median overall survival for patients with overexpression was 97 months while patients with low expression had not reached a median overall survival at their last follow up (p=0.03). This prognostic power was comparable to that provided by mutational status, and stronger than that provided by ZAP-70 or CD38 expression. Finally, in 56 patients the gene dosage as defined in QRT-PCR was inversely proportional with time to treatment (p= 0.006). This novel gene therefore has several features that make it a candidate to be the first disease specific gene identified in CLL.

scholarly journals Re-Evaluating the Prognosis and Transformation Risk of Chronic Eosinophilic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-16
Author(s):  
Daniel O'Leary ◽  
Amrita Goyal
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Acute Leukemia ◽  
Hodgkin Lymphoma ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Disease Specific Survival ◽  
Chronic Eosinophilic Leukemia ◽  
Aggressive Disease ◽  
Disease Specific

Chronic eosinophilic leukemia, not otherwise specified, (CEL-NOS) is a rare myeloproliferative neoplasm defined by an autonomous clonal expansion of eosinophil precursors. CEL-NOS has long been considered an aggressive disease with a poor prognosis and high risk of transformation to blast phase. This impression was reinforced by a case series of 10 patients with CEL-NOS in which median overall survival was 22 months and in which one half of patients transformed to acute leukemia at a median of 20 months from time of diagnosis (Helbig et al, American Journal of Hematology, 2012). However, this has not been confirmed in any population-based or large cohort studies. We sought to evaluate whether this poor prognosis is consistent across a larger patient database. We identified 487 patients with CEL-NOS in the Surveillance Epidemiology and End Result-18 database. Patients were predominantly male (60.5%) with a median age of 57 at time of diagnosis. Overall survival at 2 years from diagnosis for the cohort was 92.7% with a disease-specific survival of 97.2%. At 5 years overall survival remained relatively high (88.7%) as did disease-specific survival (95.6%). Median follow-up was 56.5 months (range 0-191 months). Median survival for patients who died of CEL was 5 months (range 0-46 months). This raises the possibility of a dichotomous patient population wherein there is one group of patients with a good prognosis, and a second group with aggressive disease and significantly poorer prognosis. Of note, the majority of the patients who died from CEL-NOS (21/23) died within two years of diagnosis. Only three of the patients studied developed acute leukemia, two with acute myeloid leukemia and one acute lymphoblastic leukemia; all three died of their second malignancy within 28-60 months. An additional 11 patients developed lymphoma, 2 Hodgkin lymphoma and 9 non-Hodgkin lymphoma (NHL), including peripheral T-cell lymphoma (3/9), diffuse large B-cell lymphoma (3/9), angioimmunoblastic T-cell lymphoma (2/9), and Burkitt's lymphoma (1/9). This data suggests that the current impression of CEL-NOS as a rare and aggressive disease with a poor prognosis may be more nuanced than previously appreciated. The limitations of SEER data are significant and include concerns regarding both accuracy of diagnosis and collection bias. However, the incongruence between current disease perception and the large-scale data available suggest that further study is both warranted and necessary. Next steps would include the creation of a prospective national registry of patients with CEL-NOS. This would assist both in giving appropriate disease-counseling for patients and in better assessing which patients might benefit from treatment with chemotherapy. Disclosures No relevant conflicts of interest to declare.

Pre-existing geriatric conditions in older adults with poor prognosis cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12044-12044
Author(s):  
Mazie Tsang ◽  
Siqi Gan ◽  
Melisa L. Wong ◽  
Louise Christie Walter ◽  
Alexander K. Smith
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Cancer Diagnosis ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Entire Cohort ◽  
Injurious Falls ◽  
Geriatric Conditions ◽  
Nationally Representative ◽  
Climbing Stairs

12044 Background: Older adults with poor prognosis cancers are more likely to experience toxicity from cancer-directed therapies. Although geriatric assessment (GA) reduces chemotherapy toxicity by detecting pre-existing conditions, GA can be difficult for oncologists to perform because of limited time and resources. We aim to determine the prevalence of pre-existing geriatric conditions that could be detected if GA were performed during routine oncology care. Methods: We used the Health and Retirement Study (HRS) linked with Medicare (1998-2016) to identify adults age >65 with poor prognosis cancers (median overall survival < 1 year). The HRS is a biennial nationally representative survey that asks about pre-existing geriatric conditions. Using the interview prior to the cancer diagnosis, we determined the presence of conditions included in GA: functional status (i.e. difficulty with climbing stairs, walking one block, getting up from a chair, bathing or showering, taking medications, and managing money), falls and injurious falls, unintentional weight loss, self-rated health, social support, mentation, advanced care planning, use of pain or sleep medications, and mobility. To identify groups with the highest prevalence of pre-existing geriatric conditions, we stratified results by age (adjusted for gender) and gender (adjusted for age). Results: Our study included 2,121 participants. At the time of cancer diagnosis, mean age was 76, 51% were female, 79% were non-Hispanic White, 26% had lung cancer, 14% had a GI cancer, and 60% had other metastatic cancers. Mean time between the HRS interview and cancer diagnosis was 12.7 months. The median overall survival of the entire cohort was 9.6 months with a 45% 1-year survival rate. The adjusted prevalence of pre-existing geriatric concerns were as follows: 65% had difficulty with climbing several flights of stairs, 27% had difficulty with walking one block, 47% had difficulty getting up from a chair after sitting down, 12% had difficulty in bathing or showering, 6% had difficulty taking medications, 11% had difficulty in managing money, 35% had a fall in the last 2 years with 12% of participants reporting injury after their fall. Those who were aged 85+, vs those aged 65-74, had higher rates of conditions indicative of cognitive impairment (e.g. 12 vs 4% had difficulty taking medications, p = 0.000, 26% vs 6% had difficulty managing money, p = 0.000) and physical impairments (e.g. 54% vs 30% had falls, respectively, p = 0.000). Rates of geriatric conditions indicative of physical impairment were higher in women vs men (e.g. 72% vs 58% had difficulty climbing stairs, p = 0.000 and 52% vs 41% had difficulty getting up from a chair, p = 0.000). Conclusions: Patients with poor prognosis cancers have high rates of pre-existing geriatric conditions that can be detected by GA. Geriatric assessments could find important impairments that could be addressed prior to cancer therapy to reduce adverse effects.

scholarly journals PROTOCOL FOR LIVER TRANSPLANTATION IN HILAR CHOLANGIOCARCINOMA

2021 ◽  
Vol 34 (3) ◽  
Author(s):  
Lucas ERNANI ◽  
Rodrigo Bronze de MARTINO ◽  
Wellington ANDRAUS ◽  
Eduardo de Souza Martins FERNANDES ◽  
Felipe Pedreira Tavares de MELLO ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Overall Survival ◽  
Large Volume ◽  
Mayo Clinic ◽  
Hilar Cholangiocarcinoma ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Clinical Use ◽  
Surgical Results ◽  
Liver Transplantations

ABSTRACT Background: Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy. Aim: To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma. Method: The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages. Result: A protocol proposal for this disease is presented, which needs to be validated for clinical use. Conclusion: The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.

Validation of the Prognostic Significance of the Disease Specific Gene CLLU1 in Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 709-709 ◽  
Author(s):  
Par Josefsson ◽  
Jesper Jurlander ◽  
Christian H. Geisler ◽  
Lone B. Pedersen ◽  
Lone Bach ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Expression Level ◽  
Specific Gene ◽  
Cd38 Expression ◽  
Mutational Status ◽  
Time To Initiation ◽  
Significant Difference ◽  
Disease Specific

Abstract We have recently identified and cloned a novel disease specific gene CLLU1, with a strong prognostic significance in a small test cohort of CLL patients (ASH 2004, #770). To validate this finding in a larger series, 176 newly diagnosed, previously untreated CLL patients referred to Rigshospitalet, Copenhagen in 1991–1999, were investigated. Clinical characteristics of the population were: 116 stage A patients (66 %), median age 69.9 years, 98 males (56%), median follow up 59 months. The end points for the statistical analysis were overall survival and time to initiation of treatment. At time of analysis 91 (52%) patients had died and 104 (59%) had commenced treatment. Frozen patient samples, taken at time of diagnosis, were investigated for CLLU1 expression, as well as for mutational status, CD38 expression, ZAP-70 expression and cytogenetic aberrations. CLLU1 expression was assayed by QRT-PCR using the cDNA1 splice variant, and expressed as fold upregulation above the CLLU1 level in normal B-cells. CD38 and ZAP-70 analysis was performed by flow cytometry, using a 20 % cut-off level. Cytogenetic analysis was performed by FISH. The previously reported (ASH 2004, #770) median upregulation of CLLU1 in CLL cells was accurately reproduced and confirmed (25.5-fold (N = 176) vs. 27.7-fold (N = 59) in test population). Also in accordance with the pilot study, segregation of the patients based on the median CLLU1 expression level divided the population in two groups with significantly different times to initiation of treatment and borderline significant difference in overall survival. However, further analysis found an optimal cut-off level at 40-fold upregulation of CLLU1 expression; use of this cut-off demonstrated a highly significant difference in overall survival for patients with upregulated expression of CLLU1 (p = 0.0023). The median overall survival was 60.2 months for patients with CLLU1 expression above 40-fold compared to 100.8 months for the group with lower expression level. Likewise the time to initiation of first treatment was significantly shorter in the high-level expression group (p = 0.0018, median time to first treatment 9.3 months vs. 54.9 months). Furthermore, CLLU1 expression was upregulated in all poor prognostic subgroups investigated: Binet stage B or C, IgVH unmutated, unfavorable cytogenetics, high CD38 expression and high ZAP-70 expression. Our new study confirms that CLLU1 is a strong prognostic factor in CLL, comparable to other established prognostic markers. The exclusive upregulation of CLLU1 expression in CLL suggests a putative role for CLLU1 in the pathogenesis of CLL, and makes this gene a strong candidate for future gene-targeted treatment strategies. Figure Figure

scholarly journals Increased expression of POLR3G predicts poor prognosis in transitional cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10281
Author(s):  
Xianhui Liu ◽  
Weiyu Zhang ◽  
Huanrui Wang ◽  
Chin-Hui Lai ◽  
Kexin Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Transitional Cell ◽  
Clinicopathological Characteristics ◽  
Pathological Stage ◽  
Qrt Pcr ◽  
Kaplan Meier ◽  
Normal Bladder ◽  
Gene Sets

Background Previous studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC. Methods The RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC. Results Transcriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT. Conclusions POLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.

scholarly journals Outcome of Patients with Double-Expressor Lymphomas (DELs) Treated with R-CHOP or R-EPOCH

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5396-5396 ◽  
Author(s):  
Anita Aggarwal ◽  
Hind Rafei ◽  
Fadi Alakeel ◽  
Antoine Nafez Finianos ◽  
Min-Ling Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
Laboratory Data ◽  
B Cell Lymphoma ◽  
World Health ◽  
Survival Curves ◽  
Kaplan Meier

Abstract Background: MYC protein is expressed in 30-50% of diffuse large B cell lymphoma (DLBCL) and is associated with concomitant expression of BCL2 in 20% to 35% of cases. DLBCLs with co-expression of MYC and BCL2 are called double-expressor lymphomas (DELs); whereas double-hit lymphomas (DHLs) have MYC and BCL2 or BCL6 rearrangement as detected by fluorescence in situ hybridization (FISH) or standard cytogenetics and are currently classified by the World Health Organization as high grade B cell lymphoma (HGBL). MYC/BCL2 double expression is an independent risk factor of DLBCL relapse or progression. In several studies, DELs were shown to have worse outcomes than other DLBCLs, but not as much aggressiveness as the DHLs (HGBL). Poor response to standard chemotherapy CHOP or R-CHOP is seen with DHLs and DELs with a median overall survival of <12 months. The purpose of this study was to characterize DELs amongst veteran patients with DLBCL and their outcomes. Methods: This is an IRB-approved, retrospective study of patients diagnosed with DLBCL between 1/1996 and 1/2016 at the Washington DC Veterans Affairs Medical Center. Sixty nine DLBCL patients were identified. All patients with unavailable tissue for pathology testing were excluded. Immunohistochemistry (IHC) stains were reviewed for CD3, CD5, CD10, CD20, CD30, BCL2, BCL6, C-MYC, MUM-1, MIB1, Cyclin-D1, and p53. DELs were defined by concomitant expression of MYC and BCL2 detected by IHC (cutoffs-30% MYC, 40% BCL2). We did not sub-classify our patients into DHLs because of unavailability of MYC and BCL2 rearrangement results by FISH. Demographic and laboratory data at diagnosis, treatment regimens and outcomes in terms of relapse and death were analyzed. Student's t-test was used to compare means and chi-square to compare proportions. Results: Sixty nine eligible cases of DLBCL were identified, 31 were excluded because of insufficient tissue for full characterization, leaving us with 38 cases for analysis. All cases were CD20 positive with high MIB1. MYC was positive in 19 cases (50%) of whom 17 were as well positive for BCL2 (44.7%) (DELs); the remaining 21 were non-DELs. Median age at diagnosis for all patients was 65 years. Stages at diagnosis for all patients were as follows: I (2 patients; 5.3%), II (8; 21.1%), III (7; 18.4%), IV (20; 52.6%). Stage and presence of extra-nodal disease were not significantly different in the DEL vs the non-DEL groups. The majority of DEL patients had an IPI score of 3 (intermediate-high) compared to a score of 2 (low-intermediate) in non-DEL patients (difference was not significant). Mean LDH at diagnosis for all patients was 365.7 ±273 IU/L (133-1285); higher in DEL (422.9±340.5) as compared to non-DEL (314±182) patients. Within the DEL group, 5 patients (29.4%) received R-CHOP; 11 (64.7%) received R-EPOCH as first line chemotherapy. Four out of the 5 (80%) treated initially with R-CHOP relapsed and eventually died. Of the 11 DEL patients treated with R-EPOCH, 2 (18.2%) relapsed and one of these two died. The relapse rate between the 2 treatment groups of DEL was significantly higher for R-CHOP (p=0.042). Of 21 non-DEL patients, 14 (66.7%) remained in remission; 2((9.5%) relapsed; and 5(23.8%) were lost-to-follow-up. Nineteen (50%) patients died and median overall survival (OS) was 18.5 months for the whole group (20.4 vs 36.1 in the DEL vs non-DEL groups respectively; no statistical significance). Conclusions: The proportion of DELs identified amongst DLBCL in our study is consistent with the literature. As expected, patients with DEL had a worse OS than non-DEL patients in our study, which is consistent with DEL's poor prognosis. Although the sample size in our study is small, there was a more favorable outcome with R-EPOCH treatment of DEL. Larger prospective and interventional studies are needed to confirm these results, develop new treatment strategies for DEL, and better characterize the underlying biology driving its poor prognosis. Figure 1 Kaplan-Meier survival curves comparing overall survival in DEL vs non-DEL groups Figure 1. Kaplan-Meier survival curves comparing overall survival in DEL vs non-DEL groups Disclosures No relevant conflicts of interest to declare.

Identification of Poor Risk Patients in Low and Intermediate-1 (Int-1) IPSS MDS with the New Ipssr Index and Comparison with Other Prognostic Indexes. A Study by the Spanish Group of MDS (GESMD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 702-702 ◽  
Author(s):  
David Valcárcel ◽  
Guillermo Sanz ◽  
Margarita Ortega ◽  
Benet Nomdedeu ◽  
Elisa Luño ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Lower Risk ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Poor Risk ◽  
Number Of Patients ◽  
Risk Patients ◽  
Md Anderson ◽  
Very High

Abstract Abstract 702 Despite that low and intermediate-1 (int-1) IPSS groups are commonly considered as low risk diseases with a median overall survival exceeding 60 months, some of these patients will evolve as higher risk myelodysplastic syndrome (MDS). Recently several new prognosis indexes (PI) have been proposed: The new IPSSr, WPSSr, MD Anderson for lower risk patients (MDA) Index, and the Spanish Group of MDS (GESMD) proposal that considers as high risk those patients with int-1 IPSS and at least one of the following: platelets <30×109/L, granulocytes <0.5×109/L, poor or very poor-risk karyotype or the presence of bone marrow (BM) fibrosis. The aim of the study was to compare the four PI and to analyze which of them was the best to identify patients with the poorest risk (defined as those with a median overall survival (OS) lower than 30 months) and to segregate different risk groups in a population of lower risk MDS patients. Indexes were compared using the Akaike analysis methodology. A total of 2410 patients from the Spanish registry of MDS with low or int-1 IPSS were included. Median age was 74 years (42.6% female). The IPSS value was of: 0, 0.5 and 1 in 1314, 761 and 335 patients, respectively. The four poor risk variables defined by the GESMD confirmed its adverse predictive value for OS: granulocytes <0.5×109/L (n=101, P<0.001), platelets <30×109/L (n=94, P<0.001), poor or very poor risk karyotype (n=35, P=0.007), and BM fibrosis (n=109 of 698 evaluable patients, P<0.001). The presence of at least one of these was associated with adverse prognosis in the int-1 group but not in the low IPSS risk group, thus only the former was considered as high risk. The distribution of patients across the four PI is detailed in the Table. These new PI identified between 16.9% and 46% of patients having a median OS of around 30 months within the int-1 patients (wide line in the table), but none of the PIs could identify such a poor prognosis patients in the low IPSS group. The PI that identified the highest number of patients with shorter OS was the new IPSSr, while MDA IP was the most discriminative in the Akaike analysis. In conclusion, IPSS is not discriminative enough in the int-1 group. In contrast, the application of the new PI can be employed to better identify poor prognosis patients within the int-1 group who could benefit from a high-risk approach. Table. Overall survival and AML evolution according to the different prognostic index. PROGNOSIS INDEX (AIC for the whole population/and for the Int-1) populations) PROGNOSIS GROUP IPSS LOW (N=1314) OS: 87.78 m (95% CI:74.5-101.0) AML EVOLUTION (3 years): 9.1% (95% CI: 6.9-11.3%) IPSS INT-1 (N= 1096) OS: 44.2 m (95% CI:39.1-49.3) AML EVOLUTION (3 years): 26.9% (95% CI: 23-30.8%) N (%) Overall Survival Median (95% CI) months AML evolution (3 years) % (95% CI) N (%) Overall Survival Median (95% CI) months AML evolution (3 years) % (95% CI) GESMD (12566.6/6425.9) LOW 1314 (100) 860 (78.5) 48.1 (40.9-55.3)* 25.1 (20.7-29.5)** HIGH 0 (0) 236 (21.5) 32.7 (39.1-49.3)* 34.3 (24.5-44.1)** MD. Anderson (12381.4/6357.2) LOW 508 (39.3) 130.3 (104.6-157.0)* 9% (5.4-12.6)! 109 (9.9) 115.2 (83.8-146.6)* 15.7 (6.5-24.9)* INT 781 (59.4) 69.7 (62.4-77.1)* 8.9% (6.9-11.9)! 653 (59.6) 51.3 (44.2-58.3)* 23.3 (18.3-28.3)* HIGH 25 (1.9) 58.4* (25.4-91.5)* ——–——–— 334 (30.5) 24.1 (19.3-28.9)* 39.9 (31.3-48.5)* IPSS-R (12409.9/6369.6) VERY LOW 690 (52.5) 118.8 (105.7-131.7)* 6.4% (4.2-8.6)*** 79 (7.2) 113.7 (39.9-187.4)* 17.8 (4.6-31)* LOW 602 (45.8) 65.9 (57.6-74.2)* 11.6% (7.8-15.4)*** 505 (46.1) 60.3 (53.3-67.2)* 18.2 (13.4-23)* INT 22 (1.7) 58.9 (25.2-92.7)* 26% (2-50)*** 416 (38) 30.5 (26.1-34.8)* 38.6 (30-47.2)* HIGH 0 (0) 95 (8.7) 21.2 (16.5-25.9)* 48.5 (32.5-64.5)* VERY HIGH 0 (0) 1 (0.1) WPSS-R (12477.4/6414.7) VERY LOW 517 (39.3) 115.2 (103.0-127.4)* 6.5 (3.7-9.3)$ 76 (6.9) 56.5 (38.2-74.9)* 22.8 (10.6-35)* LOW 524 (39.9) 78.5 (66.7-90.3)* 12.1 (7.7-15.5)$ 289 (26.4) 61.3 (48.3-74.2)* 19.2 (12.4-25.6)* INT 61 (4.6) 46.0 (30.8-61.1)* 13.7 (3.1-24.3)$ 386 (5.2) 42.5 (32.8-52.2)* 27.8 (20.8-34.8)* HIGH 3 (0.2) 185 (16.9) 24.11 (19.4-28.8)* 49.3 (35.7-62.9)* VERY HIGH 0 (0) 4 (0.4) NOT EVAL 209 (15.9) 87.8 (74.6-101.3)* 7.2 (3-11.4)$ 156 (14.2) 48 (30.8-65.2) 18.3 (9.1-27.5)* AIC: Akaike Information Criteria. Int: Intermediate, Not Eval: Not evaluable, CI: Confidence interval. * P<0.001; ** P=0.02; *** P=0.04; ! !P=0.7 $P=0.1 Figure. Actuarial curves of overall survival according to the different PI. Figure. Actuarial curves of overall survival according to the different PI. Disclosures: No relevant conflicts of interest to declare.

Reduced integrin alpha3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung.

1998 ◽  
Vol 16 (3) ◽  
pp. 1060-1067 ◽  
Author(s):  
M Adachi ◽  
T Taki ◽  
C Huang ◽  
M Higashiyama ◽  
O Doi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Overall Survival Rate ◽  
Rt Pcr ◽  
Integrin Alpha3

PURPOSE We investigated the possible association between integrin alpha3 and motility-related protein (MRP-1), cluster of differentiation antigen 9 (CD9) gene expression in non-small-cell lung cancer (NSCLC) and evaluated the prognostic significance of integrin alpha3 expression. PATIENTS AND METHODS We performed a retrospective study of integrin alpha3 and MRP-1/CD9 expression in resected tumor tissues from 151 NSCLC patients using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS The ratio of integrin alpha3/beta-actin expression ranged from 0 to 5.87 (mean was 0.80; median, 0.70). Using the cutoff value of 0.7, there were 78 (52%) integrin alpha3-positive tumors and 73 (48%) tumors with reduced integrin alpha3 expression. The immunohistochemical results agreed well with those of the RT-PCR assays, and 88% had no discrepancy. In case of discrepancy, the results of RT-PCR were used in specimen classification. Integrin alpha3 gene expression was independent from MRP-1/CD9 gene expression. No significant association was found between integrin alpha3 expression and the patients' clinical characteristics. The overall survival rate of patients with integrin alpha3-positive NSCLCs was only slightly better than that of individuals whose tumors had reduced integrin alpha3 expression (55.9% v 47.1%; P = .085). By comparison, the overall survival rate of patients with integrin alpha3-positive adenocarcinomas was strikingly greater than in those whose tumors had reduced gene expression (54.4% v 35.2%; P = .004). Multivariate analysis with the Cox regression model of NSCLC and adenocarcinoma indicated that integrin alpha3 expression correlated better (P = .0188 and P = .0008, respectively) with the overall survival rate than other variables, except lymph node status. CONCLUSION No significant association was found between integrin alpha3 and MRP-1/CD9 gene expression in lung cancer. However, reduced integrin alpha3 expression is a poor prognosis factor in patients with adenocarcinomas.

scholarly journals Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges miR-3653-3p

2020 ◽  
Author(s):  
Xudong Wang ◽  
Taiqiu Chen ◽  
Zhihuai Deng ◽  
Wenjie Gao ◽  
Tongzhou Liang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Luciferase Reporter ◽  
Specific Gene ◽  
Biological Processes ◽  
Rt Pcr ◽  
Alizarin Red ◽  
Qrt Pcr ◽  
Marrow Mesenchymal Stem Cells ◽  
Dual Luciferase Reporter Assay

Abstract Background: Little is known about the implications of circRNAs in the effects of Melatonin (MEL) on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation and osteoporosis progression.The aim of our study was to investigate circRNAs in MEL-regulated BMSCs differentiation and osteoporosis progression.Methods: BMSCs osteogenic differentiation was measured by qRT-PCR, western blot (WB), Alizarin Red and alkaline phosphatase (ALP) staining. Differential circRNA and mRNA profiles of BMSCs treated by MEL were characterized by deep sequencing, followed by validation using RT-PCR, Sanger sequencing, and qRT-PCR. Silencing and overexpression of circ_0003865 were conducted for functional investigations. The sponged microRNAs and targeted mRNAs were predicted by bioinformatics and validated by qRT-PCR, RNA pull-down, and dual-luciferase reporter assay. The function of miR-3653-3p and circ_0003865/miR-3653-3p/growth arrest-specific gene 1 (GAS1) cascade were validated for the osteogenic differentiation of BMSCs by CCK-8, qRT-PCR, WB, Alizarin Red, and ALP staining. The effects of circ_0003865 on osteoporosis (OP) development was tested in murine osteoporosis model.Results: MEL promoted osteogenic differentiation of BMSCs. RNA sequencing revealed significant alterations in circRNA and mRNA profiles associated with multiple biological processes and signaling pathways. Circ_0003865 expression in BMSCs was significantly decreased by MEL treatment. Silencing of circ_0003865 had no effect on proliferation while promoted osteogenic differentiation of BMSCs. Overexpression of circ_0003865 abrogated the promotion of BMSCs osteogenic differentiation induced by MEL, but proliferation of BMSCs induced by MEL had no change whether circ_0003865 was overexpression or not. Furthermore, circ_0003865 sponged miR-3653-3p to promote GAS1 expression in BMSCs. BMSCs osteogenic differentiation was enhanced by miR-3653-3p overexpression while BMSCs proliferation was not affected. By contrast, miR-3653-3p silencing mitigated the promoted BMSCs osteogenic differentiation caused by circ_0003865 silencing, but had no effect on proliferation. Finally, circ_0003865 silencing repressed OP development in mouse model.Conclusion: MEL promotes BMSCs osteogenic differentiation and inhibits osteoporosis pathogenesis by suppressing the expression of circ_0003865, which regulates GAS1 gene expression via sponging miR-3653-3p.

Outcome analysis of primary liver carcinomas.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 438-438
Author(s):  
Maria Majella Doyle ◽  
Neeta Vachhajarani ◽  
Nael Saad ◽  
Kathryn Fowler ◽  
Benjamin R. Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Outcome Analysis ◽  
Single Center ◽  
Limited Series ◽  
Tumor Types ◽  
Disease Free ◽  
Disease Specific ◽  
Prospective Database

438 Background: Treatments for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCCa) are established. Significant debate exists over optimal treatment for biphenotypic primary liver carcinomas (PLC) with combined HCC and IHCCa (B-PLC) and is considered to be a contraindication for transplantation. The purpose of this analysis is to determine single center outcomes of patients with B-PLC compared to HCC and IHCCa. Methods: A prospective database was reviewed to determine treatments and survivals of patients with HCC, IHCCa and B-PLC. Results: From 1/1/2009 to 12/31/2014, 810 patients with PLC were treated with resection (LRx) (n = 117), liver transplant (OLT) (n = 224) or liver directed therapy (LDT) (n = 469). 723 patients had HCC, 34 had IHCCa and 53 had B-PLC. Overall Survival (OS) in the LDT group, was similar comparing all tumor types at 1 yr (61.7%) and 3 yrs. (23.8%) (p =.3) Median survival (MS) was 16.2 months. OS in the LRx group was also similar between tumor types (1yr 81.1% and 5yrs. 41.1%, p =.2) and MS was 40.9 months. Comparing OLT patients with HCC (n = 212, 77% within Milan) to B-PLC (n = 10, 70% within Milan), OS (1yr 92.5% and 5 yrs. 77.0%, p =.8) was comparable and so also were disease-specific (1yr 99.0% and 5yr 97.3%, p =.6) and disease-free (1yr 88.7% and 5yrs. 73.5%, p =.4) survivals. OS for patients with B-PLC was significantly greater in patients receiving OLT vs. LRx or LDT (p =.005). Conclusions: Biphenotypic PLC has a poor prognosis and has been considered a contraindication for OLT. In this limited series, however, outcomes with transplantation appear acceptable.

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