Evaluation of liver kinase B1 downstream signaling expression in various breast cancers and relapse free survival after systemic chemotherapy treatment

Maintenance therapy containing Methotrexate (MTX) and 6-Mercaptopurine (6MP) is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides (TGN) into DNA (DNA-TG), and higher leucocyte DNA-TG is associated with increased relapse-free survival. As 6-Thioguanine (6TG) provides 6-fold higher cytosol TGN than 6MP, we added low-dose 6TG to MTX/6MP maintenance therapy to explore if this combination results in significantly higher DNA-TG. Target population of the “Thiopurine Enhanced ALL Maintenance therapy” (TEAM) study was n=30 patients, with non-high risk ALL, aged 1–45 years on MTX/6MP maintenance therapy receiving no other systemic chemotherapy. Incremental doses of 6TG were added to MTX/6MP maintenance therapy (start 6TG: 2.5 mg/m2/day, maximum: 12.5 mg/m2/day). Primary endpoint was DNA-TG increments. Thirty-four patients were included, and 30 patients completed maintenance therapy according to TEAM strategy. Of these 30 patients, 26 (87%) tolerated 10.0–12.5 mg/m2/day as maximum 6TG dose. TEAM resulted in significantly higher DNA-TG, when compared with both TEAM patients before TEAM inclusion (on average 251 fmol/μg DNA higher (95% CI 160–341; P<0.0001), and with historical patients receiving standard MTX/6MP maintenance therapy (on average 272 fmol/μg DNA higher (95% CI 147–398; P<0.0001). TEAM did not increase myelotoxicity or hepatotoxicity. Conclusively, TEAM is an innovative and feasible approach to improve maintenance therapy and results in higher DNA-TG without inducing additional toxicity. It may therefore be an effective strategy to reduce risk of ALL relapse through increased DNA-TG, and this will be tested in a randomized ALLTogether-1 substudy.

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

npj Breast Cancer ◽

10.1038/s41523-021-00238-4 ◽

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.

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A low number of tumor infiltrating FOXP3-positive cells after primary systemic chemotherapy is correlated with favorable relapse-free survival in breast cancer patients.

10.1158/0008-5472.sabcs-5043 ◽

2009 ◽

Author(s):

T Aruga ◽

E Suzuki ◽

S Horiguchi ◽

K Horiguchi ◽

S Sekine ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Systemic Chemotherapy ◽

Breast Cancer Patients ◽

Relapse Free Survival ◽

Free Survival ◽

Primary Systemic Chemotherapy

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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

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Trattamento Radiante Elettivo del Carcinoma Mammario

Tumori Journal ◽

10.1177/030089168206800113 ◽

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.

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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.

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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.

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