Expression of p63 protein in pulmonary adenocarcinomas as factor of poor prognosis

Aim. To study the spectrum of cellular molecular-biological markers and identify those of them that can be used as prognostic factors for the clinical course of pulmonary adenocarcinoma. Material and Methods. In the given work archive material of 129 patients with confirmed diagnosis of pulmonary adenocarcinoma was used. In the work, histological, immunohistochemical, molecular-genetic and statistical methods were used. Results. In 29 cases (47.5%) of pulmonary adenocarcinoma, focal cytoplasmic and/or nuclear expression of p63 protein was observed in different proportions of cells. With expression of p63 in tumor cells, relapse-free survival was on average 25.7±5.1 months, while in patients with no expression of р63 it was 26.1±2.8 months. This parameter did not influence the overall survival of patients which was on average 33.6±2.7 months. Conclusion. A weak tendency to reduction of relapse-free survival of patients with p63-positive pulmonary carcinoma of lungs was revealed. Identification of p63 in pulmonary adenocarcinoma may be regarded as a factor of unfavorable prognosis and of risk of faster tumor progression, which requires further study to increase the statistical value of research.

Download Full-text

Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival

Annals of Hematology ◽

10.1007/s00277-021-04413-2 ◽

2021 ◽

Author(s):

Juan Tong ◽

Lei Zhang ◽

Huilan Liu ◽

Xiucai Xu ◽

Changcheng Zheng ◽

...

Keyword(s):

Myeloid Leukemia ◽

Poor Prognosis ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Relapse Free Survival ◽

Free Survival ◽

Chemotherapy Group ◽

Blood Transplantation ◽

The Poor ◽

First Complete Remission

AbstractThis is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1–2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4–89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89–37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0–83.6%), which was significantly higher than the 10% (95% CI, 5.72–35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0–46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8–98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0–41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2–76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

Download Full-text

BT-09 CLINICAL AND MOLECULAR GENETIC FEATURE OF CEREBELLAR GLIOBLASTOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.170 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii37-ii38

Author(s):

Shohei Iijima ◽

Kuniaki Saito ◽

Saki Shimizu ◽

Keiichi Kobayashi ◽

Daisuke Shimada ◽

...

Keyword(s):

Clinical Course ◽

Molecular Genetic ◽

Progression Free Survival ◽

Tumor Location ◽

Cerebellar Hemisphere ◽

Free Survival ◽

Specific Pcr ◽

Cerebellar Glioblastoma ◽

Number Variation ◽

Dependent Probe

Abstract INTRODUCTION Cerebellar glioblastoma (cGBM) is extremely rare, accounting for 0.7–0.9% of all gliomas. Few studies have reported on clinical course, histopathology, and prognosis. In this report, we discussed cases which were diagnosed as cGBM, and were treated in our institute. Materials and Methods We retrospectively analyzed 9 cGBMs (age ranged 41 to 85 years, median 69), operated at our institute after 2010 January, and evaluated their <MGMT> promoter methylation, <IDH1> mutation, and Copy Number Variation status detected by methylation-specific PCR (MSP), DNA sequencing or immunohistochemistry, and Multiplex Ligation-dependent Probe Amplification (MLPA), respectively. RESULTS All patients underwent resection; 3 gross total resections (GTRs, 33%), 2 subtotal resections, 4 partial resections, with relatively low achievement of GTR. The tumor location predominated in the cerebellar hemisphere (7 patients, 78%) over vermis (2). One patient had brain stem invasion. After surgery, 8 patients received temozolomide (TMZ) and radiotherapy (RT), while did only one RT alone. After recurrence, three patients were treated with bevacizumab monotherapy, and other three received either TMZ and RT, TMZ and ACNU, or TMZ monotherapy. The median progression-free survival (PFS) was 12.0 months, and the median overall survival (OS) was 17.1 months. Five patients (56%) were <MGMT> methylated, whereas all were <IDH1>wild-type. <PTEN> deletion was negative in all patients. <EGFR> amplification and combined <PDGFR> amplification and <CDKN2A> deletion were found in one patient each. DISCUSSION Despite the lower rate of GTR, there was a tendency of longer PFS compared to supratentorial GBM (sGBM). The clinical course after recurrence was unfavorable, and OS thereafter was similar to that of sGBM. cGBMs appeared to lack the typical genetic mutations occurred in sGBM, suggesting that cGBMs might be stimulated with different regulatory cellular signals.

Download Full-text

THE rs2200733 POLYMORPHISM ON CHROMOSOME 4q25 AFFECTS THE EFFICIENCY OF PULMONALY VEIN ISOLATION IN PATIENTS IN ATRIAL FIBRILLATION

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-11-119-126 ◽

2020 ◽

pp. 119-126

Author(s):

Aksyutina N.V. ◽

Shulman V.A. ◽

Aldanova E.E. ◽

Kusaev V.V.

Keyword(s):

Atrial Fibrillation ◽

Molecular Genetic ◽

Pulmonary Veins ◽

Genetic Research ◽

Early Recurrence ◽

Russian Population ◽

Relapse Free Survival ◽

Free Survival ◽

Number Of Patients ◽

First Time

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, accounting for 1-2% in the general population. Currently, such a method of surgical treatment of AF as catheter ablation of the orifices of the pulmonary veins (CA PVV) is widely used. In the foreign literature in recent years, the results of single studies have appeared, which showed a clear association between the rs2200733 polymorphism and the occurrence of AF relapses after CA PVV. Such studies have not been conducted on the Russian population. Purpose of the study: to determine the relationship between the rs2200733 polymorphism of chromosome 4q25 and the efficiency of CA PVV in AF. A total of 113 patients with primary AF and 134 with secondary AF were examined. Control - 182 healthy people. A subgroup of 67 people was formed, with the conducted CA PVV from patients with primary AF. Conducted: ECG, EchoCG, Holter ECG monitoring, VEM, CAG, molecular genetic research. Among patients with recurrent AF after CA PVV, the TT genotype was detected statistically significantly more often than in patients without recurrence (20.00% relative to 0.00%, p<0.05), while if there is a genotype with the T allele, the risk of AF recurrence increased 3.6 times (OR 3.636; CI 95% 1.324-9.991). The median relapse-free survival (which represents the time during which AF relapse occurs in 50% of patients) is 12.00 ± 0.66 months in the presence of the CT genotype (95% CI 10.70-13.30), 11.00 ± 2.99 months in patients with the TT genotype (95% CI 5.14-16.86). The median relapse-free survival was not determined in patients with the CС genotype, since the number of patients without signs of relapse of the disease was more than 50% by the end of the observation period. In this study, for the first time in the Russian population, it has been shown that the TT genotype and the T allele of the rs2200733 polymorphism are predictors of early recurrence of AF after CA PVV.

Download Full-text

Loss Of H3K27 Trimethylation (H3K27me3) Associates With a Multi Drug Resistance Phenotype In Acute Myeloid Leukemia (AML)

Blood ◽

10.1182/blood.v122.21.1253.1253 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1253-1253

Author(s):

Stefanie Göllner ◽

Tino Schenk ◽

Sven Stengel ◽

Christian Rohde ◽

Tim Sauer ◽

...

Keyword(s):

Drug Resistance ◽

Protein Expression ◽

Mrna Expression ◽

Histone Modifications ◽

Poor Prognosis ◽

Therapy Resistance ◽

Relapse Free Survival ◽

Free Survival ◽

Knock Down ◽

Ezh2 Expression

Abstract Histone modifications play a crucial role in the regulation of gene expression by activating or inactivating transcription. The Polycomb Group Protein Enhancer of Zeste Homologue 2 (EZH2) mediates trimethylation of histone H3K27, thereby inducing gene silencing. Overexpression of EZH2 has been reported to be associated with metastases and cancer progression in solid tumors like breast cancer or prostate cancer. However, loss of function mutations or deletions of EZH2 occur in myeloid malignancies and T-ALL. These mutations result in a poor prognosis. The aim of this study was to analyze the relevance of histone modifications for therapy resistance in AML. FLT3-ITD positive MV4-11 leukemic cells that were continuously cultured in media containing the kinase inhibitor PKC412 became resistant not only to PKC412 but also to standard chemotherapeutics Cytarabin (AraC) and Daunorubicin. Western blot analysis identified an almost complete loss of H3K27me3 in resistant MV4-11 cells (MV4-11R). This was accompanied by loss of EZH2 protein in the MV4-11R compared to the sensitive MV4-11. To test for acquisition of drug resistance due to reduced H3K27me3 levels, lentiviral knock-down (KD) of EZH2 was performed in the sensitive MV4-11 leading to diminished H3K27me3 levels. Knock-down cells showed resistance to the apoptosis-inducing effects of PKC412 compared to scrambled controls. Furthermore, resistance to standard chemotherapeutics AraC and Daunorubicin could be also observed in MV4-11 KD cells compared to control. To verify whether diminished levels of H3K27me3 can cause a more general, FLT3-ITD-independent drug resistance, knock-down of EZH2 was performed in FLT3-WT AML cell lines HL60, Kasumi-1 and ML-1. Again, this led to resistance to the standard chemotherapeutics AraC and Daunorubicin. In order to investigate the regulation of EZH2 in MV4-11R, promoter methylation and microRNA expression analysis was performed revealing no regulation of EZH2 expression via both mechanisms. Instead, the reduction of EZH2 protein expression was depended on posttranslational mechanisms that could be counteracted by CDK1-inhibitors. CDK1-inhibitors restored EZH2 protein and H3K27 trimethylation levels as well as drug sensitivity. By analyzing EZH2 mRNA expression of 220 primary diagnosed AML patients, a trend towards low EZH2 mRNA expression and poor overall as well as relapse free survival could be demonstrated. Thus, EZH2- and H3K27me3 protein expression were also analyzed by immunohistochemistry in bone marrow biopsies from AML patients (N=126). H3K27me3 and EZH2 protein expression correlated closely (r= 0.9, p<0.001). Low H3K27me3 levels indicated a poor prognosis with significantly decreased overall (median 11.06 vs. 38.6 months, p=0.017), event-free (median 4 vs. 19.9 months, p=0.014) and relapse-free survival (median 10 versus 31.2 months, p=0.038) compared to patients with high H3K27me3 protein expression. Similar findings were obtained for the loss of EZH2 protein. EZH2 low/absent expression was associated with a significantly decreased overall (median 9.6 vs. 47.6 months, p=0.018), event-free (median 4.06 vs. 46 months, p=0.013) and relapse-free survival (median 11.3 versus 55.3 months, p=0.47) compared to patients with high EZH2 protein expression. Taken together, these data indicate that loss of EZH2 expression and reduction of H3K27me3 levels induce widespread therapy resistance in AML and associate with a poor prognosis in AML patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Increased Serum Level of MicroRNA-663 Is Correlated with Poor Prognosis of Patients with Nasopharyngeal Carcinoma

Disease Markers ◽

10.1155/2016/7648215 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Shaoqiang Liang ◽

Ning Zhang ◽

Yanming Deng ◽

Lusi Chen ◽

Yang Zhang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Serum Level ◽

Poor Prognosis ◽

Clinical Stage ◽

Serum Levels ◽

Malignant Progression ◽

Healthy Controls ◽

Clinical Factors ◽

Relapse Free Survival ◽

Free Survival

MicroRNAs (miRs) play crucial roles in the carcinogenesis and malignant progression of human cancers including nasopharyngeal carcinoma (NPC). In this study, we aimed to investigate the association of serum miR-663 levels with the clinical factors and prognosis of NPC patients. Real-time PCR was performed to examine the amount of miR-663 in serum in NPC patients and healthy controls. Our data showed that the amount of miR-663 in serum was significantly higher in NPC patients than in healthy controls. Moreover, the serum levels of miR-663 were significantly correlated with the grade, lymph node metastasis, and clinical stage of NPC. Furthermore, higher serum miR-663 levels were closely associated with worse 5-year overall survival (OS) and relapse-free survival (RFS) of patients with NPC, and the serum level of miR-663 was found to be an independent predicator for the prognosis of NPC. In addition, after receiving chemoradiotherapy, the serum levels of miR-663 were significantly reduced in NPC patients. In summary, miR-663 was upregulated in the serum of NPC patients, which was downregulated after chemoradiotherapy, and its increased levels were closely associated with malignant progression and poor prognosis in NPC patients. Therefore, the amount of miR-663 in serum may become a potential predicator for the clinical outcome of NPC patients.

Download Full-text

Co-expression of mesothelin and CA125/MUC16 is a prognostic factor for breast cancer, especially in luminal-type breast cancer patients

Biomarker Research ◽

10.1186/s40364-021-00335-3 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Takahiro Einama ◽

Yoji Yamagishi ◽

Yasuhiro Takihata ◽

Takafumi Suzuki ◽

Tamio Yamasaki ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Independent Predictor ◽

Prognostic Significance ◽

Breast Cancer Patients ◽

Relapse Free Survival ◽

Free Survival ◽

Poor Patient ◽

Luminal Type

AbstractThe expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the expression of mesothelin and CA125, and the clinicopathological meaning and prognosis of the co-expression of mesothelin and CA125 in breast cancer. Our results showed that among 478 patients, mesothelin and CA125 were co-expressed in 48 (10 %), mesothelin only in 75 (16 %), CA125 only in 217 (45 %), and neither in 234 (49 %). A high correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with poor patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. In conclusion, this is the first to report the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of mesothelin and CA125 may be clinically useful for prognostication after surgical therapy in patients with breast cancer.

Download Full-text

A comparative study of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.9.1303 ◽

1989 ◽

Vol 7 (9) ◽

pp. 1303-1309 ◽

Cited By ~ 38

Author(s):

A Borg-Grech ◽

J A Radford ◽

D Crowther ◽

R Swindell ◽

M Harris

Keyword(s):

Comparative Study ◽

Hodgkin's Disease ◽

Clinical Course ◽

Hodgkin’S Disease ◽

Relapse Free Survival ◽

Mixed Cellularity ◽

Free Survival ◽

Clinical Behavior ◽

Phenotypic Differences ◽

Nodular Sclerosing

A clinical comparison of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease (HD-LP) has shown them to be similar in all respects, including survival and relapse-free survival (RFS). In addition, they appear similar to mixed cellularity (MC) and nodular sclerosing Hodgkin's disease (HD-NS) with regard to clinical course. Thus, the reported phenotypic differences between nodular lymphocyte predominant Hodgkin's disease (HD-LP[N]) and other forms of the disease do not appear to be reflected in clinical behavior.

Download Full-text

Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival

BMC Cancer ◽

10.1186/1471-2407-13-562 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 8

Author(s):

Andri Rezano ◽

Kazuhiko Kuwahara ◽

Mutsuko Yamamoto-Ibusuki ◽

Masahiro Kitabatake ◽

Penpak Moolthiya ◽

...

Keyword(s):

Poor Prognosis ◽

Breast Cancers ◽

Relapse Free Survival ◽

Free Survival

Download Full-text

Surgery and metastases of stomach cancer in liver

Medical alphabet ◽

10.33667/2078-5631-2020-29-21-24 ◽

2020 ◽

pp. 21-24

Author(s):

F. M. Dzhuraev ◽

S. L. Gutorov ◽

E. I. Borisova ◽

G. G. Khakimova

Keyword(s):

Gastric Cancer ◽

Liver Metastases ◽

Lymphovascular Invasion ◽

Peritoneal Dissemination ◽

Surgical Removal ◽

Relapse Free Survival ◽

Cancer Markers ◽

Free Survival ◽

The Poor ◽

Isolated Liver

Liver metastases of gastric cancer determine the poor prognosis. Until now The expediency of their surgical removal has been controversial. However, according to a number of studies, the removal of potentially operable isolated liver metastases allows a significant increase of overall and relapse-free survival in some cases. The review is dedicated to the analysis of prognostic factors that allow selecting patients for surgical removal of liver metastases of gastric cancer. The main criteria are: effective perioperative chemotherapy; stage under T4, N0, absence of lymphovascular invasion, absence of peritoneal dissemination, number less than 3, size up to 4 cm, localization of metastases in one lobe, low level of cancer markers CA 19-9 and CEA.

Download Full-text

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

Orvosi Hetilap ◽

10.1556/650.2015.30260 ◽

2015 ◽

Vol 156 (45) ◽

pp. 1824-1833 ◽

Cited By ~ 1

Author(s):

Árpád Illés ◽

Ádám Jóna ◽

Zsófia Simon ◽

Miklós Udvardy ◽

Zsófia Miltényi

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Treatment Options ◽

Survival Rates ◽

Relapse Free Survival ◽

Term Survival ◽

Free Survival ◽

Novel Treatment ◽

Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

Download Full-text