scholarly journals Uncovering the Exosomes Diversity: A Window of Opportunity for Tumor Progression Monitoring

2020 ◽  
Vol 13 (8) ◽  
pp. 180 ◽  
Author(s):  
Domenico Maisano ◽  
Selena Mimmi ◽  
Rossella Russo ◽  
Antonella Fioravanti ◽  
Giuseppe Fiume ◽  
...  

Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring.

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3711
Author(s):  
François Montagne ◽  
Florian Guisier ◽  
Nicolas Venissac ◽  
Jean-Marc Baste

Non-small cell lung cancers (NSCLC) are different today, due to the increased use of screening programs and of innovative systemic therapies, leading to the diagnosis of earlier and pre-invasive tumors, and of more advanced and controlled metastatic tumors. Surgery for NSCLC remains the cornerstone treatment when it can be performed. The role of surgery and surgeons has also evolved because surgeons not only perform the initial curative lung cancer resection but they also accompany and follow-up patients from pre-operative rehabilitation, to treatment for recurrences. Surgery is personalized, according to cancer characteristics, including cancer extensions, from pre-invasive and local tumors to locally advanced, metastatic disease, or residual disease after medical treatment, anticipating recurrences, and patients’ characteristics. Surgical management is constantly evolving to offer the best oncologic resection adapted to each NSCLC stage. Today, NSCLC can be considered as a chronic disease and surgery is a valuable tool for the diagnosis and treatment of recurrences, and in palliative conditions to relieve dyspnea and improve patients’ comfort.


1996 ◽  
Vol 75 (3) ◽  
pp. 171-173 ◽  
Author(s):  
Gordon Soo ◽  
Anthony Chan ◽  
Dennis Lam ◽  
Victor Abdullah ◽  
C. Andrew van Hasselt

A case of extramedullary plasmacytoma with its unusual appearance is reported. This is the second reported case in world literature affecting the paranasal sinuses with intracranial extension. The role of surgery is to obtain tissue for diagnosis and to excise residual disease. Radiotherapy is the treatment of choice and long-term follow-up is necessary for monitoring disease recurrence. The overall 10-year survival is about 50%. The case is discussed with a general review of the management of this pathology.


1990 ◽  
Vol 8 (6) ◽  
pp. 1036-1041 ◽  
Author(s):  
M Nardi ◽  
F Cognetti ◽  
C F Pollera ◽  
M D Giulia ◽  
A Lombardi ◽  
...  

A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal (IP) recombinant alpha-2-interferon (r-alpha 2-IFN) and cisplatin (DDP) as salvage therapy for less than or equal to 5 mm residual-disease (RD) ovarian carcinoma. Fourteen assessable patients entered the study. All had received prior chemotherapy (11 with DDP-based regimens); five patients had macroscopic RD (less than or equal to 5 mm), and nine had microscopic RD (histologically positive random biopsies and/or positive cytology and immunocytochemical tests). The response to IP immunochemotherapy was evaluated by laparotomy. Pathologic complete remissions (PCRs) were achieved in seven patients (50%) who have remained free of disease with a median follow-up of 22+ months (range, 11+ to 30+ months). Six patients achieved a stable disease and one presented disease progression. With the exception of chemical peritonitis-induced adhesions, no limiting toxicity was observed. The results obtained in this small, highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous (IV) DDP. Larger comparative studies must be conducted to establish the potential role of IP DDP and r-alpha 2-IFN as compared with either of the single treatments.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2001-2001
Author(s):  
Carmen Balana ◽  
Carlos Mesia Barroso ◽  
Sonia Del Barco Berron ◽  
Estela Pineda Losada ◽  
José Muñoz-Langa ◽  
...  

2001 Background: The GEINO-14-01 trial (NCT02209948) investigated the role of extending temozolomide (TMZ) for 6 cycles after the standard 6 cycles to improve 6m-PFS, SLP and OS in newly diagnosed glioblastoma (GBM) patients (p). Methods: Between 08/2014 and 11/2018, 166 p were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment for 6 cycles after proving stable disease in the MRI performed before inclusion. Centralized review of histology and determination of MGMT status, if not previously available, were performed before randomizing patients. Two criteria of stratification were used: MGMT status and presence/absence of residual disease on the basal MRI (defined as a residual enhancement larger than 1cm in one). The primary endpoint was differences in 6mPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results: Median age was 60.3 (range 29-83), 97p (61%) were methylated, basal MRI showed residual disease in 57p (35.8%). After a median follow up of 14.0 months, with 121 p(76.1%) already progressed and 81p (50.9%) already dead, median PFS is presented. Median (m) PFS is 8.0 months (95%CI: 5.7-10.2). There is no difference in mPFS between arms (adjusted HR = 0.98, 95% CI: 0.82-1.18, P = 0.907). Methylated tumors had longer mPFS (HR=0.57, 95% CI: 0.39-0.83, P=0.004) irrespectively to the study treatment. Conclusions: There is not apparent benefit of continuing TMZ treatment for more than 6 cycles. Data will be actualized for the congress.Supported by a Grant of the ISCIII: PI13/01751. Clinical trial information: NCT02209948.


Author(s):  
Guillaume Richard-Carpentier ◽  
Hagop M Kantarjian ◽  
Guilin Tang ◽  
C. Cameron Yin ◽  
Joseph D. Khoury ◽  
...  

Acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23) - KMT2A-AFF1 is associated with a poor prognosis. The impact of KMT2A rearrangements other than t(4;11) is uncertain and the benefit of allogeneic stem cell transplant (HSCT) is unclear. We reviewed adult patients with ALL treated at our institution from 1984 to 2019 and identified 50/1102 (5%) with KMT2A rearrangement: 42 (84%) with t(4;11)/KMT2A-AFF1 and 8 (16%) with other gene partners. The median age was 45 years old (range, 18 - 78 years); median white blood cell count was 109.0 x 109/L (range, 0.5 - 1573.0). The complete remission (CR) rate was 88% and the rate of measurable residual disease negativity by flow cytometry at CR was 41% (76% overall during follow-up). At the last follow-up, 14 patients were alive. The 5-year overall survival (OS) rate was 18% (95% CI, 9 - 35%) with no difference between t(4;11) and other KMT2A rearrangements (p=0.87). In a 4-month landmark analysis, the 5-year OS rate was 32% (95% CI, 14 - 70%) in patients who underwent HSCT versus 11% (95% CI, 3 - 39) in others (p=0.10). Our study confirms the poor prognosis of ALL with any KMT2A rearrangement and the role of HSCT in these patients.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8004-8004 ◽  
Author(s):  
H. S. Hochster ◽  
E. Weller ◽  
R. D. Gascoyne ◽  
T. Ryan ◽  
T. M. Habermann ◽  
...  

8004 Background: To determine optimal induction and the role of maintenance, the E1496 study randomized patients (pts) to induction CVP (cyclophosphamide, vincristine, prednisone) versus CF (cyclophosphamide 1 G/m2 d1, fludarabine 20 mg/m2 d1–5 every 28 d) for 2 cycles beyond best response (maximum 8). Responding and stable pts were secondarily randomized to MR (375 mg/m2 weekly × 4 every 6 months for 2 years [yr]) or observation (OBS). Methods: Due to early deaths the CF arm was closed to accrual with 115 pts randomized to CF and 119 pts to CVP (thereafter all pts were assigned to CVP prior to maintenance randomization). The results presented here compare the outcome of CF patients with the subset of E1496 pts randomized to CVP (CVPR). Results: Median follow-up on pts randomized to induction is 6.5 yr. Toxic deaths occurred in 8 (7%) CF pts during induction and 4 additional deaths (1 OBS, 3 MR) occurred among the 69 (6%) CF pts randomized to MR or OBS. Causes of death were infection (9), liver failure (2), CNS gliosis (1). CF pts received a median of 5 cycles compared to 7 cycles for CVPR. The CR rate was 51% vs 22% (p=0.00001) and the PR rate was 35% vs 55% for CF vs. CVPR, respectively. Four-yr PFS for CF vs. CVPR was 49% vs 45% (p=0.19) and OS was 66% vs. 81% (p=0.12), respectively. Of 45 CF deaths, 23 (51%) occurred without lymphoma progression compared to 5 (13%) of 38 CVPR deaths (p=0.0004). More than 90% of CF patients randomized to maintenance achieved protocol-defined minimal residual disease compared with 64% CVPR pts. Maintenance therapy had no impact on 2 yr PFS for the 67 evaluable randomized CF pts, which was 74% for MR vs. 73% for OBS (p=0.19). In contrast, 2 yr PFS was 73% for MR and 42% for OBS in randomized CVPR pts (p=0.004). Survival at 2 yr for MR vs OBS was: CF 79% vs 91% (p=0.19) compared with CVP 98% vs 93% (p=0.21). Conclusions: Induction with CF results in higher CR and miminal residual disease rates than CVP. However, gains in remission quality with CF (in the dose and schedule used here) were offset by early and late deaths in the absence of progressive lymphoma. In E1496, the benefit of MR was influenced by the induction chemotherapy. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6046-6046 ◽  
Author(s):  
Rachel Soyoun Kim ◽  
Manjula Maganti ◽  
Marcus Bernardini ◽  
Stephane Laframboise ◽  
Sarah E. Ferguson ◽  
...  

6046 Background: The role of intraperitoneal (IP) chemotherapy in the management of advanced ovarian cancer has been questioned given emerging evidence showing lack of survival benefits. The objective of this study was to compare the long-term survival associated with IP chemotherapy at a tertiary cancer center. Methods: We reviewed the long-term survival records of 271 women with stage IIIC or IV high-grade serous ovarian cancer treated with primary cytoreductive surgery (PCS) followed by IP or intravenous (IV) chemotherapy between 2001-2015 with a minimum follow-up of 4 years. 5-year progression free (PFS) and overall survival (OS) rates were compared using Kaplan-Meier survival analysis and covariates were evaluated using Cox regression analysis. Results: Women who received IP chemotherapy after PCS (n = 91) were more likely to have undergone aggressive surgery (p < 0.001), longer surgery (p < 0.001), and had no residual disease (p < 0.001) compared to the IV arm (n = 180). Median follow-up was 51.6 months. Five-year PFS was 19% vs. 18% (p = 0.63) and OS was 73% vs. 44% (p = 0.00016) in the IP vs. IV arms, respectively. After controlling for covariates in a multivariable model, the use of IP was no longer a significant predictor of OS in the entire cohort (p = 0.12). In patients with 0mm residual disease, PFS was 28% vs. 26% (p = 0.67) and OS was 81% vs. 60% (p = 0.059) in IP (n = 61) vs. IV (n = 69), respectively. In patients with residual of 1-9mm, PFS was 30% vs. 48% (p = 0.076) and OS was 60% vs. 43% (p = 0.74) in IP (n = 29) vs. IV (n = 31), respectively. Conclusions: IP chemotherapy showed a trend towards improved survival over conventional IV chemotherapy, especially in patients with no residual disease. Given the retrospective nature and small numbers in this study, prospective non-randomized cohort studies are warranted to evaluate the role of IP chemotherapy in advanced ovarian cancer.


2019 ◽  
Vol 20 (11) ◽  
pp. 2840 ◽  
Author(s):  
Marta Zarà ◽  
Gianni Francesco Guidetti ◽  
Marina Camera ◽  
Ilaria Canobbio ◽  
Patrizia Amadio ◽  
...  

Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their formation, EVs associate with specific cargo from their parental cell that can include RNAs, free fatty acids, surface receptors, and proteins. The biological function of EVs is to maintain cellular and tissue homeostasis by transferring critical biological cargos to distal or neighboring recipient cells. On the other hand, their role in intercellular communication may also contribute to the pathogenesis of several diseases, including thrombosis. More recently, their physiological and biochemical properties have suggested their use as a therapeutic tool in tissue regeneration as well as a novel option for drug delivery. In this review, we will summarize the impact of EVs released from blood and vascular cells in arterial and venous thrombosis, describing the mechanisms by which EVs affect thrombosis and their potential clinical applications.


1998 ◽  
Vol 14 (3) ◽  
pp. 155-160 ◽  
Author(s):  
Salah T. Fayed ◽  
Samira M. Ahmad ◽  
Samar K. Kassim ◽  
Ali Khalifa

The role of the tumor markers CA125 and CA72-4 has been evaluated in the diagnosis and management of ovarian cancer. Both markers were measured in 30 patients with proven epithelial ovarian cancer, 30 patients with benign pelvic masses and 30 normal women. CA125 and CA72-4 were measured using the luminometric immunoassay and immuno-radiometric assay respectively. All patients with ovarian cancer were submitted to surgical staging and cytoreduction followed by adjuvant platinum based chemotherapy for 3–6 courses. Fixing the specificity at 95%, CA125 had a sensitivity of 76.7% at a cut-off 85u/ml while CA72-4 had a sensitivity of 70% at a cut-off 8.5 u/ml. The combination of CA72-4 with CA125 increased the sensitivity to 95% while fixing the specificity at 95%. Among seven cases with stage I and II ovarian cancer five cases had CA125 level below 85 U/ml, three patients out of them had CA72-4 above 8.5 U/ml. CA 72-4 could reflect the residual disease following cytoreduction and could improve the detection of relapse by CA125.Conclusion: CA72-4 could complement the standard tumor marker CA125 both in diagnosis and follow up of patients with epithelial ovarian cancer.


2014 ◽  
Vol 24 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Valentin Kolev ◽  
Elena B. Pereira ◽  
Myron Schwartz ◽  
Umut Sarpel ◽  
Sasan Roayaie ◽  
...  

ObjectiveThe aim of this study is to determine the role of liver metastatectomy in the morbidity and survival of patients with recurrent ovarian carcinoma.MethodsWe retrospectively reviewed the records of all patients who had undergone hepatic resection for liver metastases from ovarian carcinoma at the time of cytoreductive surgery at our institution from 1988 to 2012. The Kaplan-Meier method was used for survival analysis. A total of 76 patients met the inclusion criteria and had undergone liver resection as part of cytoreductive surgery for ovarian carcinoma during the study period. Of these 76 patients, 27 underwent liver resection at the time of secondary cytoreduction, and these patients that are the focus of this analysis.ResultsMedian overall survival for the study group from the time of diagnosis to the last follow-up or death was 56 months (range, 12–249 months). Twenty died of the disease with an overall median survival of 12 months from the time of the liver resection (2–190 months), and 7 patients were alive with the disease at the time of the last follow-up. Based on Kaplan-Meier survival analysis, the factors associated with the longest survival after the liver resection (2–190 months) were the interval from the primary surgery of less than 24 months versus more than 24 months (P= 0.044) and secondary cytoreduction to residual disease of less than 1 cm (P= 0.014).ConclusionsBased on our analysis of a single institution’s series of ovarian cancer patients with hepatic metastasis, liver resection is feasible and safe and should be considered as an option in selected patients at the time of secondary cytoreduction.


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