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

BMC Cancer ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Andri Rezano ◽  
Kazuhiko Kuwahara ◽  
Mutsuko Yamamoto-Ibusuki ◽  
Masahiro Kitabatake ◽  
Penpak Moolthiya ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Breast Cancers ◽  
Relapse Free Survival ◽  
Free Survival

scholarly journals 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

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.

scholarly journals CYP19Genetic Polymorphism HaplotypeAASAIs Associated with a Poor Prognosis in Premenopausal Women with Lymph Node-Negative, Hormone Receptor-Positive Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sung-Hsin Kuo ◽  
Shi-Yi Yang ◽  
Huang-Chun Lien ◽  
Chiao Lo ◽  
Ching-Hung Lin ◽  
...  
Keyword(s):  
Lymph Node ◽  
Hormone Receptor ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Breast Cancers ◽  
Free Survival ◽  
Receptor Status ◽  
Premenopausal Patients ◽  
Disease Free

Given the critical role ofCYP19in estrogen synthesis, we investigated the influence ofCYP19gene polymorphisms on the clinical outcome of lymph node- (LN-) negative, hormone receptor- (HR-) positive early breast cancers. Genotyping for theCYP19polymorphisms rs4646 (A/C), rs1065779 (A/C),CYP19(TTTA)n (short allele/long (S/L) allele using the 7 TTTA repeat polymorphism as the cut-off), and rs1870050 (A/C) was performed on 296 patients with LN-negative, HR-positive breast cancers. All patients received adjuvant hormonal therapy. Associations were examined between these 4 genotypes and 6 common haplotypes ofCYP19and distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS). Patients were divided into the 6 subhaplotypes ofCCLA(41.1%),AASA(17.1%),CASA(11.9%),CCLC(8.9%),CCSA(7.5%),AASC(8.9%), and others (4.6%). In premenopausal patients, haplotypeAASAwas significantly associated with a poor DDFS (adjusted hazard ratio (aHR), 3.3;P=0.001), DFS (aHR, 2.5;P=0.0008), and OS (aHR, 2.9;P=0.0004) after adjusting for age, tumor size, tumor grade, estrogen receptor status, progesterone receptor status, chemotherapy, pathology, adjuvant hormone therapy, menopausal status, and radiotherapy. Furthermore, haplotypeAASAremained a negative prognostic factor for premenopausal patients receiving adjuvant chemotherapy in terms of DDFS (aHR, 4.5;P=0.0005), DFS (HR, 3.2;P=0.003), and OS (HR, 6.4;P=0.0009). However, in postmenopausal patients, haplotypeAASAwas not associated with a poor prognosis, whereas theAASChaplotype was significantly associated with a poor DFS (aHR, 3.1;P=0.03) and OS (aHR, 4.4;P=0.01). Our results indicate that, in patients with LN-negative, HR-positive breast cancers, genetic polymorphism haplotypeAASAis associated with poor survival of premenopausal women but does not affect survival of postmenopausal women.

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

Blood ◽  
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.

scholarly journals Co-dependency for MET and FGFR1 in basal triple-negative breast cancers

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Vanessa Y. C. Sung ◽  
Jennifer F. Knight ◽  
Radia M. Johnson ◽  
Yaakov E. Stern ◽  
Sadiq M. Saleh ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Triple Negative ◽  
Tumour Progression ◽  
Patient Stratification ◽  
Breast Cancers ◽  
Poor Clinical Outcome ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Dual Inhibition

AbstractTriple-negative breast cancer (TNBC) is a heterogeneous disease that lacks both effective patient stratification strategies and therapeutic targets. Whilst elevated levels of the MET receptor tyrosine kinase are associated with TNBCs and predict poor clinical outcome, the functional role of MET in TNBC is still poorly understood. In this study, we utilise an established Met-dependent transgenic mouse model of TNBC, human cell lines and patient-derived xenografts to investigate the role of MET in TNBC tumorigenesis. We find that in TNBCs with mesenchymal signatures, MET participates in a compensatory interplay with FGFR1 to regulate tumour-initiating cells (TICs). We demonstrate a requirement for the scaffold protein FRS2 downstream from both Met and FGFR1 and find that dual inhibition of MET and FGFR1 signalling results in TIC depletion, hindering tumour progression. Importantly, basal breast cancers that display elevated MET and FGFR1 signatures are associated with poor relapse-free survival. Our results support a role for MET and FGFR1 as potential co-targets for anti-TIC therapies in TNBC.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
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.

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

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.

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

2019 ◽  
Vol 27 (3) ◽  
pp. 315-324
Author(s):  
Maria M. Byakhova ◽  
Alexey A. Glazkov ◽  
Igor Yu. Vinogradov ◽  
George A. Frank
Keyword(s):  
Poor Prognosis ◽  
Clinical Course ◽  
Molecular Genetic ◽  
Pulmonary Adenocarcinoma ◽  
Relapse Free Survival ◽  
Free Survival ◽  
The Given ◽  
Weak Tendency ◽  
Molecular Biological Markers ◽  
Archive Material

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.

Trattamento Radiante Elettivo del Carcinoma Mammario

1982 ◽  
Vol 68 (1) ◽  
pp. 73-80
Author(s):  
Carlo Nervi ◽  
Giorgio Arcangeli ◽  
Donatella Tirindelli Danesi ◽  
Giovanni Creton
Keyword(s):  
Breast Cancer ◽  
Distant Metastases ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Breast Cancers ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Negative Prognostic Factor ◽  
Intercurrent Disease

From March 1972 to November 1979 a total of 157 patients with stage I to III primary breast cancers have been irradiated after segmental resection (12 cases), tilectomy (89 cases) or biopsy (56 cases). Complete local control was achieved in all Stage I lesions, in 97 % Stage II lesions and in 68 % Stage III lesions. Non recurrence has been observed in patients previously operated by segmental resections, while local failures occurred in 6/89 and in 16/56 patients operated by tilectomy or biopsy, respectively. Of the 28 Stage I patients, 24 (86 %) are alive, one with distant metastases. Four patients of this group are dead, 2 of intercurrent disease and 2 of breast cancer. Of the 61 (Stage II) patients, 38 (62 %) are alive, 5 of these with distant metastases. Twenty-three patients are dead, 15 with active disease, and 8 suffered intercurrent death. Of the 68 Stage III patients, 21 (31 %) are alive, 6 of these with distant metastases. Fourty-seven patients are dead, 43 of breast cancer and 4 of intercurrent disease. The high probability of initial subclinical deposits is evidenced by the fact that 49 of the 68 patients in this group developed distant metastases. The patients with T1 lesions appear to comprise the most favourable group with a relapse free survival at five years of 76 %. The 5 years relapse free survival was 62 % for T2 lesions and 25 % for T3 and T4 lesions. N0 status does not confer the same favourable prognosis as T1 status. N+ status, however, resulted in a definitly negative prognostic factor. Cosmetic results after our treatment approach appear to be extremely good. A marked difference between the irradiated and controlateral breast occurred only in 10 of the 125 patients after a minium of 2 years observation.

Surgery and metastases of stomach cancer in liver

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.

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