scholarly journals The role of Survivin as a biomarker and potential prognostic factor for breast cancer

2019 ◽  
Vol 65 (6) ◽  
pp. 893-901 ◽  
Author(s):  
Glaucia Luciano da Veiga ◽  
Raissa Daniel Machado da Silva ◽  
Edimar Cristiano Pereira ◽  
Ligia Ajaime Azzalis ◽  
Beatriz da Costa Aguiar Alves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chemotherapeutic Agents ◽  
Primary Health ◽  
Common Cancer ◽  
Non Melanoma Skin Cancer ◽  
Potential Prognostic Factor ◽  
Current Scenario ◽  
Melanoma Skin

SUMMARY Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

scholarly journals Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

2021 ◽  
Vol 22 (18) ◽  
pp. 9926
Author(s):  
Evangelia Ioannidou ◽  
Michele Moschetta ◽  
Sidrah Shah ◽  
Jack Steven Parker ◽  
Mehmet Akif Ozturk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Chemotherapeutic Agents ◽  
Combination Therapies ◽  
Mechanisms Of Resistance ◽  
Marginal Benefit ◽  
Antiangiogenic Activity ◽  
Castration Resistant ◽  
Common Cancer

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.

scholarly journals A Novel Role of IGF1 in Apo2L/TRAIL-Mediated Apoptosis of Ewing Tumor Cells

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Frans van Valen ◽  
Henning Harrer ◽  
Marc Hotfilder ◽  
Uta Dirksen ◽  
Thomas Pap ◽  
...  
Keyword(s):  
De Novo ◽  
Fumonisin B1 ◽  
Chemotherapeutic Agents ◽  
Ceramide Synthase ◽  
Short Term ◽  
Igf1 Receptor ◽  
Induced Apoptosis ◽  
Survival Effect

Insulin-like growth factor 1 (IGF1) reputedly opposes chemotoxicity in Ewing sarcoma family of tumor (ESFT) cells. However, the effect of IGF1 on apoptosis induced by apoptosis ligand 2 (Apo2L)/tumor necrosis factor (TNF-) related apoptosis-inducing ligand (TRAIL) remains to be established. We find that opposite to the partial survival effect of short-term IGF1 treatment, long-term IGF1 treatment amplified Apo2L/TRAIL-induced apoptosis in Apo2L/TRAIL-sensitive but not resistant ESFT cell lines. Remarkably, the specific IGF1 receptor (IGF1R) antibodyα-IR3 was functionally equivalent to IGF1. Short-term IGF1 incubation of cells stimulated survival kinase AKT and increased X-linked inhibitor of apoptosis (XIAP) protein which was associated with Apo2L/TRAIL resistance. In contrast, long-term IGF1 incubation resulted in repression of XIAP protein through ceramide (Cer) formation derived from de novo synthesis which was associated with Apo2L/TRAIL sensitization. Addition of ceramide synthase (CerS) inhibitor fumonisin B1 during long-term IGF1 treatment reduced XIAP repression and Apo2L/TRAIL-induced apoptosis. Noteworthy, the resistance to conventional chemotherapeutic agents was maintained in cells following chronic IGF1 treatment. Overall, the results suggest that chronic IGF1 treatment renders ESFT cells susceptible to Apo2L/TRAIL-induced apoptosis and may have important implications for the biology as well as the clinical management of refractory ESFT.

scholarly journals P334 Tofacitinib for the treatment of Ulcerative Colitis: Analysis of malignancy rates from the Ulcerative Colitis clinical programme

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S357-S359
Author(s):  
R C Ungaro ◽  
M A Ciorba ◽  
G Rogler ◽  
A I Sharara ◽  
N Sunna ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Incidence Rates ◽  
Open Label ◽  
Non Melanoma Skin Cancer ◽  
Daily Dose ◽  
Adjudication Committee ◽  
Necrosis Factor ◽  
Maintenance Study ◽  
Melanoma Skin

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated analysis of adjudicated malignancies in the tofacitinib UC clinical programme, including final data from the open-label, long-term extension (OLE) study (as of 24 Aug 2020). Methods Malignancies were evaluated from 3 randomised, placebo-controlled studies (2 Phase [P]3 induction studies [NCT01465763; NCT01458951]; 1 P3 maintenance study [NCT01458574]) and an OLE study (NCT01470612). Three cohorts were analysed: Induction (P3 induction studies), Maintenance (P3 maintenance study) and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P3 or OLE studies; data from the previous data cut [May 2019] are also reported for comparison). Analysis was by predominant dose (PD) 5 or 10 mg BID, based on average daily dose <15 mg or ≥15 mg, respectively (82.1% of patients received PD 10 mg BID). An independent adjudication committee reviewed potential malignancies. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) were evaluated for malignancies (excluding non-melanoma skin cancer [NMSC]) and NMSC. Results 1124 patients were evaluated for malignancies (2809.4 patient-years of tofacitinib exposure; up to 7.8 years of treatment; median duration of 685.5 days). No malignancies (excluding NMSC) occurred in Induction Cohort patients. Malignancies (excluding NMSC) occurred in 1 Maintenance Cohort patient (who was receiving placebo) and in 25 Overall Cohort patients (IR 0.86 [95% confidence interval (CI) 0.56, 1.27]: PD tofacitinib 5 mg BID n=5, IR 0.63 [95% CI 0.20, 1.47]; PD tofacitinib 10 mg BID n=20, IR 0.95 [95% CI 0.58, 1.46]); 5 new cases since May 2019 (Table).1 NMSC events in the Induction and Maintenance Cohorts were previously reported (Table).1 NMSC events occurred in 21 Overall Cohort patients (IR 0.73 [95% CI 0.45, 1.12]): PD tofacitinib 5 mg BID n=5, IR 0.63 (95% CI 0.21, 1.48); PD tofacitinib 10 mg BID n=16, IR 0.77 (95% CI 0.44, 1.25); 2 new cases since May 2019 (Table).1 Conclusion There was no apparent clustering of types of malignancy, excluding NMSC. Malignancies (excluding NMSC) and NMSC IRs remained stable over time, being comparable to those previously reported in the tofacitinib UC clinical programme.1 In this analysis, malignancies (excluding NMSC) and NMSC IRs were similar to those in patients with UC treated with tumour necrosis factor inhibitors, as reported from claims data (IRs of 0.63 and 1.69, respectively).2 References

Long-term echocardiographic assessment of descendants of gestational breast cancer patients exposed to anthracycline-based chemotherapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oneto Fernandez ◽  
R Gonzalez-Manzanares ◽  
C Garcia-Duran ◽  
D Mesa Rubio ◽  
M Ruiz Ortiz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Control Group ◽  
Case Group ◽  
Breast Cancer Patients ◽  
Third Trimester ◽  
Common Cancer ◽  
Echocardiographic Parameters ◽  
Echocardiographic Assessment ◽  
Anthracycline Dose

Abstract Background Breast cancer is the most common cancer in women and the leading cause of cancer death in women. Although gestational breast cancer (GBC) accounts only for a small amount of diagnosis, the incidence is increasing due to delayed childbearing. Treating GBC is a significant challenge, having to maintain a balance between effective treatment for the patient and safety for the descendants. Anthracycline-based chemotherapy (AC) remains to be the systemic treatment of choice in many GBC patients. Although AC in GBC appears to be safe for the descendants, data on the long-term cardiotoxic effects of AC are scarce. Purpose To evaluate long-term cardiotoxicity on descendants of GBC patients exposed to AC during pregnancy or breastfeeding. Methods We retrospectively recruited descendants of GBC patients and classified them according to AC exposure (case group and non-exposed control group). We performed a thorough echocardiographic assessment. Results We identified 7 GBC patients that received AC during pregnancy (n=6) or breastfeeding (n=1). All of them were diagnosed during the second or third trimester. Median cumulative anthracycline dose was 508mg/m2. A total of 8 cases and 5 controls were recruited. Median age at echocardiographic assessment was 10 years in cases and 8 years in controls. None of them had known prior cardiac disease. Echocardiographic parameters were within normal values in both groups (Table 1). Conclusion A long-term echocardiographic assessment showed no abnormalities in a series of descendants of GBC exposed to AC during pregnancy or breastfeeding. This study may contribute to a better understanding of the safety for the descendants of AC during pregnancy or breastfeeding. Funding Acknowledgement Type of funding source: None

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