scholarly journals FISH-Guided Evaluation of Hyperdiploidy and Other Cytogenetic Abnormalities in Childhood Burkitt Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1444-1444
Author(s):  
Georgia Avgerinou ◽  
Maria Filippidou ◽  
Ioannis V Kostopoulos ◽  
Athanasios Exarchos ◽  
Kalliopi Stefanaki ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Research Funding ◽  
Clonal Evolution ◽  
Clinical Stage ◽  
Stage Iv ◽  
Genetic Profile ◽  
Advanced Clinical Stage ◽  
Diagnostic Biopsy ◽  
Myc Gene ◽  
Affected Tissue

Abstract Background: Burkitt lymphoma (BL) is the most common lymphoma in childhood. Apart from MYC rearrangement, considered the hallmark of the disease, BL often presents with additional chromosome aberrations, the biological and clinical significance of which is not fully understood. Materials and methods: The study included 72 children (55 boys, 17 girls), aged 2-16 years (median 9), with BL diagnosed on the basis of histopathology and a demonstrable MYC rearrangement. Touch imprints from the diagnostic biopsy samples were investigated with i-FISH for MYC, BCL2, BCL6, IGH, IGK and IGL rearrangements genes and copy number aberrations involving 1q21/1p32, 7cen/7q31, 9cen/9p21, 13q14/13q34 and 17cen/17p13. Deviations from the diploid status were further investigated for aneusomies of the carrier chromosome with the use of appropriate chromosome enumeration probes. Results: MYC gene was demonstrated in all cases with MYC/IGH fusion in 83.3% (60/72). 47 cases (65.3%) were found with least one additional aberration, most commonly with 1q gain (29.2%), 7q gain (19.4%), 13q deletion (19.4%), hemizygous 9p loss (8.3%) and hyperdiploidy (8.3%). Advanced clinical stage (IV), 7q gain (but not trisomy 7) and -9/9p- were significantly associated with shorter overall survival. There was no instance of relapse or death among the hyperdiploid cases. Conclusions: This extensive FISH investigation on imprints of affected tissue provides clinically meaningful information on the genetic profile of BL and may prove valuable in the management of patients with no karyotype available. In particular, the demonstration of hyperdiploidy through the use of chromosome enumeration probes could offer the means for the delineation of clonal evolution pathways and the recognition of a subgroup of children with excellent prognosis who could be cured with low-intensity chemotherapy regimens. Disclosures Kattamis: VIFOR: Consultancy; CRISPR/Vertex: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; BMS/Celgene: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy.

scholarly journals Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

2021 ◽  
Author(s):  
Marc Hendricks ◽  
Annibale Cois ◽  
Jennifer Geel ◽  
Jan du Plessis ◽  
Mairi Bassingthwaighte ◽  
...  
Keyword(s):  
Germ Cell ◽  
South African ◽  
Economic Status ◽  
Clinical Stage ◽  
Elevated Serum ◽  
Treatment Protocol ◽  
Stage Iv ◽  
Germ Cell Tumours ◽  
Advanced Clinical Stage ◽  
Risk Of Death

OBJECTIVE  To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol.METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy proven MEGCTs from birth up to and including 16 years of age. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (HR 0.284 p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p<0.001). CONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

Limited-Stage Mantle Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5330-5330 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Dai Chihara ◽  
Naoko Asano ◽  
Ken Ohmachi ◽  
Tomohiro Kinoshita ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Advanced Stage ◽  
Limited Stage ◽  
Stage Disease

Abstract [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.

scholarly journals The Fate of Patients with Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5413-5413
Author(s):  
Pavel Otahal ◽  
Andrea Janikova ◽  
David Belada ◽  
Vit Prochazka ◽  
Heidi Mocikova ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Clinical Stage ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
First Line ◽  
Advisory Committees ◽  
Advanced Clinical Stage ◽  
Line Therapy

Abstract Background: The outcome of DLBCL patients is improving, it however seems to be very poor for those who are refractory to the therapy. We have decided to analyze this group of patients. Methodology: As part of an observational clinical study NiHiL (GovTrial No NCT03199066) we identified the patients treated in the first line by R-CHOP like immunochemotherapy who met at least one criterium: 1. refractory (stable disease - SD or progression) on 1st line therapy (1st l- R), 2. refractory (SD or progression) on salvage (platinum based regimen) (Salv-R), 3. refractory to or relapse/progression within 12 months after ASCT (ASCT-R/R). There were 210 patients diagnosed in the period 2001-2017 who fulfilled the criteria. Progression-free survival (PSF) and overall survival (OS) were estimated from the time of determination of a refractory disease. Results: The cohort consisted of 163 patients primarily resistant to the first-line therapy, 31 patients were resistant to the salvage therapy and 16 patients progressed within 12 months after ASCT . At the time of the diagnosis, the median age was 65 years (22-91) (the same as at the refractory disease), 54% were males, 74% had advanced clinical stage (III+IV), 68% had IPI >3, 77% had above-normal LDH, and 45% had a tumor mass >10cm. The OS from the time of determination of refractory disease was 0.53 years, median PFS was 0.29 years. Patients under 65 years had median survival 0.8 years compared to 0.4 years in the group of patients above 65 years of age. The median PFS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.3, 0.26 and 0.35 years resp. and 5y survival 22%, 0% and 6% resp. The median OS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.55, 0.39 and 0.65 y resp. and 5y survival was 28%, 0% and 13% resp. Our results demonstrate that resistant DLBCL has an extremely poor prognosis, clearly new effective therapeutic strategies such as CAR-based therapies or others are required. This work was supported by a research program Progres Q28-9. Disclosures Belada: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Clinicopathological Differences Between Asian and Western Patients with De Novo Diffuse Large B Cell Lymphoma Treated with R-CHOP

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2665-2665
Author(s):  
Natalie Sinclair ◽  
Brady E Beltran ◽  
Moo-Kon Song ◽  
Ivana Ilic ◽  
Sirpa Leppa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Advanced Clinical Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2665 Introduction: Little is known on the racial differences in characteristics and outcomes of patients with a diagnosis with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-containing regimens. The aim of this retrospective study is to compare the clinicopathological characteristics, prognostic factors and outcomes of Asian and Western patients with a diagnosis of de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Patients and Methods: Patient-level data was collected from 8 centers (USA, Italy, Sweden, Finland, Croatia, Japan, Korea and China). This study was approved by the Institutional Review Board at each of the participant centers. All patients were diagnosed with de novo DLBCL and treated with R-CHOP administered every 3 weeks. HIV-positive and primary brain DLBCL were excluded. The requested clinical data included age, sex, performance status, lactate dehydrogenase (LDH) levels, number of extranodal sites, clinical stage, expression of CD10, BCL6 and MUM1/IRF4, response to chemotherapy, outcome and overall survival (OS). Patients were divided in Asian and Western, according to the country of report. Comparison between groups was performed with Mann-Whitney and Chi square tests for continuous and categorical variables, respectively. Univariate survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional-hazard regression test. P-values of <0.05 were considered statistically significant. Results: A total of 712 patients, 455 Asian and 257 Western patients were included in this study. Western patients were more likely to present with elevated LDH levels (70% vs. 48%; p<0.001), advance clinical stage (58% vs. 49%; p=0.02) and a non-germinal center immunohistochemical profile (53% vs. 43%; p=0.01). Additionally, Western patients were more likely to present with low risk IPI scores (p=0.003 for trend), and had higher complete response (CR) rates (91% vs. 76%; p<0.001). There were no statistical differences between the 2 groups on age at diagnosis, sex distribution, ECOG performance status, number of extranodal sites, overall response rates and proportion of deaths. After a median follow-up of 36 months, there was no difference in median overall survival (OS; not reached in both groups) or estimated 5-year OS (66% vs. 62%; p=0.67) (Figure). In the univariate analyses, ECOG >1, elevated LDH levels and advanced clinical stage were significantly associated with a worse median OS in Westerners (p<0.01 each factor) while ECOG >1, >1 extranodal sites and advanced clinical stage were significant adverse factors for Asians (p<0.01 each factor). In the multivariate analyses, ECOG >1 and advanced clinical stage were independent prognostic factors associated with a worse median OS in Westerners and Asians (p<0.01, p=0.03, and p<0.01, p<0.01, respectively). Elevated LDH level was an adverse independent prognostic factor for Western patients only (p=0.04). Conclusions: Asian and Western patients with de novo DLBCL present with distinct clinical and pathological characteristics, and although the CR rate to standard R-CHOP was higher in Westerners than in Asians, the final outcome, prognostic factors and median and 5-year OS rates are similar in both populations. Disclosures: Castillo: GlaxoSmithKline: Research Funding; Millennium Pharmaceuticals: Research Funding.

The significance of CO2 combining power in predicting prognosis of patients with stage II and III colorectal cancer

2019 ◽  
Vol 13 (13) ◽  
pp. 1071-1080 ◽  
Author(s):  
Sheng Li ◽  
Liangjun Zhu ◽  
Xianfeng Cheng ◽  
Qianyu Wang ◽  
Jifeng Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Medical Records ◽  
Retrospective Cohort ◽  
Clinical Stage ◽  
Venous Blood ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Advanced Clinical Stage ◽  
Free Survival ◽  
Disease Free

Aim: This study was to evaluate whether CO2CP level in venous blood could predict prognosis of patients with colorectal cancer (CRC). Materials & methods: A retrospective cohort of 238 patients with CRC who received surgical resection and 176 CRC Stage IV patients were included. A total of 114 healthy people were recruited as control. CO2CP levels were obtained from medical records. Survival analysis was performed to evaluate CO2CP predictive potential. The patients were divided into CO2CP high or low group based on CO2CP optimal cut-off values. Conclusion: The decreased CO2CP in CRC patients was associated with advanced clinical stage, and suggested that decreased CO2CP may predict the worse outcomes of disease-free survival in II/III stage CRC patients.

scholarly journals Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

2021 ◽  
Author(s):  
Marc Hendricks ◽  
Annibale Cois ◽  
Jennifer Geel ◽  
Jan du Plessis ◽  
Mairi Bassingthwaighte ◽  
...  
Keyword(s):  
Germ Cell ◽  
South African ◽  
Economic Status ◽  
Clinical Stage ◽  
Elevated Serum ◽  
Treatment Protocol ◽  
Stage Iv ◽  
Germ Cell Tumours ◽  
Advanced Clinical Stage ◽  
Risk Of Death

OBJECTIVE To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol. METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (OR 2.26; p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p<0.001). Forty-one patients (18.9%) died: 37 (16.9%) from disease progression, three (1.9%) from infection, two (0.9%) from chemotherapy toxicity and one (0.5%) from surgical complications. CONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level >33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of a new national protocol aims to standardise care across the socio-economic divide.

scholarly journals Interleukin-6 Differential Expression in Cancer Patients of Different Clinical Stages; a Possible Biomarker of Cancer Progression

2021 ◽  
Author(s):  
Abosede Obafunke Bello ◽  
John Abiodun Obadipe ◽  
Oluwabanke Temitope Adewusi ◽  
Anthony Oluwamuyiwa Ayanshina
Keyword(s):  
Cancer Patients ◽  
Differential Expression ◽  
Cancer Progression ◽  
Interleukin 6 ◽  
Clinical Stage ◽  
Stage Iv ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cancer Stage ◽  
Advanced Clinical Stage

Abstract PurposeThe study investigated interleukin-6 expression pattern across all stages of cancer. The research questions raised in the study were: Is there differential expression of Interleukin-6 across all cancer stages? and what relationship exists between serum interleukin-6 level and cancer stage?Methods The prospective case-control study comprised sixty two (62) purposively selected cancer participants across all stages and age range 18 years to 72years as well equal number of healthy volunteers from two medical centres in Nigeria. Three milliliters (3mls) of blood samples was collected intravenously from the participants and centrifuged after 30 minutes of collection at 3000rpm for 10 minutes to obtain serum. The serum level of Interleukin-6 was determined spectrophotometrically by Enzyme linked immunosorbent assay (ELISA). Data obtained were expressed as mean and standard error of the mean. One way Analysis of variance and t-test were employed to test for significance difference between the groups and the significant level was considered at P< 0.05. ResultsFindings from the study revealed significant (P< 0.05) higher mean serum interleukin-6 levels in stage IV cancer participants as compared to other disease stages. In the same way, significant higher mean Interleukin-6 level of stage III cancer participants as compared to that of stage I cancer participants was observed. Furthermore, the study revealed a significant correlation (P< 0.01) between serum Interleukin 6 concentration and cancer stage.Conclusion Serum interleukin-6 had differential expression in cancer patients at advanced clinical stage as compared to that of early disease stage.

scholarly journals Understanding the Role of Hyperdiploidy in Burkitt Lymphoma of Childhood: Biological and Clinical Correlates

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5296-5296
Author(s):  
Georgia Avgerinou ◽  
Stefanos Papadhimitriou ◽  
Kalliopi Stefanaki ◽  
Antonis Kattamis ◽  
Katerina Katsibardi ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Chromosome Region ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Molecular Cytogenetics ◽  
Myc Gene ◽  
Numerical Aberrations ◽  
Chromosome Regions

Abstract Background: Burkitt lymphoma (BL) is the most common high-grade lymphoma in childhood. BL is typically associated with rearrangement of the MYC gene, on 8q24 chromosome region, and often accompanied by other aberrations, some of which are known to adversely influence the clinical behavior and prognosis of the disease. However, hyperdiploidy, though frequently detected cytogenetically, has not been convincingly linked to specific biological and clinical features of BL. We present here our experience with 8 pediatric hyperdiploid BL cases detected with molecular cytogenetics in the course of routine genetic investigation. Materials and methods: The study included 44 children (35 boys, 9 girls), aged 1 to 15 years (median 6), diagnosed with histologically documented BL. In all cases, interphase FISH was performed on infiltrated bone marrow smears or touch imprints from samples of involved sites. FISH probes employed included sets of the detection MYC, BCL2, BCL6, IGH, IGK, and IGL rearrangement, -17/del(17p13), -9/(del9p21) and del(13q14)/del(13q34). Cases with over-representation of any of the chromosome regions targeted were further tested with the use of the appropriate centromeric/chromosome enumeration probe. Thus, this line of testing allowed for the detection of numerical aberrations of chromosomes 2, 3, 8, 9, 13, 14, 17, 18 and 22. Over-representation of at least three chromosomes, without evidence for any monosomy, was considered a hyperdiploidy criterion. Results: MYC was found rearranged in all cases, in 38 together with IGH and in 6 of them with IGK or IGL rearrangment. 17p-, 13q- and 9p- were detected in 3, 4 and 2 cases, respectively. There were no cases with BCL2 or BCL6 rearrangements. With a median follow-up of 5.5 years, 4 relapses/deaths were observed. Hyperdiploidy was detected in 8 patients (18.2%), with involvement of at least 7 of the 9 chromosomes tested, at the level of trisomy to hexasomy. Hyperdiploid and non-hyperdiploid cases were comparable with regard to sex and age. However, all cases with IGK/IGL involvement, 17p-, 13q- or 9p-, and relapse/death were seen exclusively in the non-hyperdiploid group. Conclusions: From the observations on this small group of patients, it seems that hyperdiploidy is rather common in childhood BL and, perhaps, represents a distinct clonal evolution pathway of the standard t(8;14)+ disease. It appears to be associated with a favorable prognosis. Further study on a larger number of cases is required to fully elucidate the clinical significance of the hyperdiploidy and whether it may be used as a marker of "low-risk" disease, by analogy to acute lymphoblastic leukemia. Disclosures Kattamis: Novartis: Consultancy, Honoraria; Vifor Pharma: Consultancy; CELGENE: Consultancy, Honoraria; ApoPharma: Honoraria.

CD8+CD28− in Peripheral Blood of Patients with Cutaneus T-Cell Lymphoma (CTLC) in Different Clinical Stages.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4395-4395
Author(s):  
Donata M. Urbaniak-Kujda ◽  
Katarzyna L. Kapelko-Slowik ◽  
Bozena Jazwiec ◽  
Joanna Maj ◽  
Jaroslaw Dybko ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Early Stage ◽  
Clinical Stage ◽  
Influence Factors ◽  
Stage Iv ◽  
Suppressor Cells ◽  
Control Group ◽  
Advanced Clinical Stage ◽  
Clinical Stages

Abstract Background: Patients with CTLC usually have a poor immune response. CD8+CD28− T cells are new types of immune suppressor cells. The study was to analyze the level and changes of them in peripheral blood with CTLC, their effects on immunosupression of CTLC, the influence factors to provide reference for treatment of CTLC patients. Patients and Methods: 27 patients with CTLC were enrolled in the study: 8 women and 19 men aged 35–81, medium 57. According to Ann Arbor classification stage I was represented by 1 patient, stage II -6 patients, stage III - 5 patients, stage IV - 6 patients and stage early stage (premycoticus) was represented by 8 patients. Peripheral blood samples were assessed from all patients with CTLC before treatment and 8 normals. Percentage CD8+CD28− T cells was analyzed by flow cytometry. Result: Compared with control group percentage of CD8+CD28− T cells was significantly higher in patients group p=0,005 (test U Mann Whitney). There were no significant differences of T-cells in among patients with different clinical stages. We revealed the correlation between CD8+CD28− cells and advanced clinical stage r=0,54, p=0,035 (Spearman correlation test). Conclusion: Percentage of CD8+CD28− T cells is increased in peripheral blood in CTLC patients, and correlates with advanced stage.

scholarly journals Basal and Luminal Molecular Subtypes in Naturally-Occurring Canine Urothelial Carcinoma are Associated with Tumor Immune Signatures and Dog Breed

2021 ◽  
pp. 1-17
Author(s):  
Breann C. Sommer ◽  
Deepika Dhawan ◽  
Audrey Ruple ◽  
José A. Ramos-Vara ◽  
Noah M. Hahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Tumor Characteristics ◽  
Rna Seq ◽  
Advanced Clinical Stage ◽  
Naturally Occurring ◽  
Immune Signatures

BACKGROUND: Improved therapies are needed for patients with invasive urothelial carcinoma (InvUC). Tailoring treatment to molecular subtypes holds promise, but requires further study, including studies in pre-clinical animal models. Naturally-occurring canine InvUC harbors luminal and basal subtypes, mimicking those observed in humans, and could offer a relevant model for the disease in people. OBJECTIVE: To further validate the canine InvUC model, clinical and tumor characteristics associated with luminal and basal subtypes in dogs were determined, with comparison to findings from humans. METHODS: RNA sequencing (RNA-seq) analyses were performed on 56 canine InvUC tissues and bladder mucosa from four normal dogs. Data were aligned to CanFam 3.1, and differentially expressed genes identified. Data were interrogated with panels of genes defining luminal and basal subtypes, immune signatures, and other tumor features. Subject and tumor characteristics, and outcome data were obtained from medical records. RESULTS: Twenty-nine tumors were classified as luminal and 27 tumors as basal subtype. Basal tumors were strongly associated with immune infiltration (OR 52.22, 95%CI 4.68–582.38, P = 0.001) and cancer progression signatures in RNA-seq analyses, more advanced clinical stage, and earlier onset of distant metastases in exploratory analyses (P = 0.0113). Luminal tumors were strongly associated with breeds at high risk for InvUC (OR 0.06, 95%CI 0.01 –0.37, P = 0.002), non-immune infiltrative signatures, and less advanced clinical stage. CONCLUSIONS: Dogs with InvUC could provide a valuable model for testing new treatment strategies in the context of molecular subtype and immune status, and the search for germline variants impacting InvUC onset and subtype.

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