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1.
Mol Cancer ; 23(1): 172, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174949

RESUMO

Exosomes mediate cell-to-cell crosstalk involving a variety of biomolecules through an intricate signaling network. In recent years, the pivotal role of exosomes and their non-coding RNAs cargo in the development and progression of several cancer types clearly emerged. In particular, tumor bulk and its microenvironment co-evolve through cellular communications where these nanosized extracellular vesicles are among the most relevant actors. Knowledge about the cellular, and molecular mechanisms involved in these communications will pave the way for novel exosome-based delivery of therapeutic RNAs as well as innovative prognostic/diagnostic tools. Despite the valuable therapeutic potential and clinical relevance of exosomes, their role on sarcoma has been vaguely reported because the rarity and high heterogeneity of this type of cancer. Here, we dissected the scientific literature to unravel the multifaceted role of exosomal non-coding RNAs as mediator of cell-to-cell communications in the sarcoma subtypes.


Assuntos
Comunicação Celular , Exossomos , RNA não Traduzido , Sarcoma , Humanos , Exossomos/metabolismo , Exossomos/genética , Sarcoma/genética , Sarcoma/patologia , Sarcoma/terapia , Sarcoma/metabolismo , RNA não Traduzido/genética , Animais , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Biomarcadores Tumorais/genética , Pesquisa Translacional Biomédica
2.
Int J Mol Sci ; 22(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34681807

RESUMO

Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence. Indeed, for years, ES survival rates have remained stagnant, suggesting that conventional treatments should be revised and improved. New therapeutic approaches are focused to target the key regulators of signaling pathways, the causative markers of tumor pathophysiology. To this end, we selected, among the drugs to which an ES cell line is highly sensitive, those that target signaling pathways known to be dysregulated in ES. In particular, we found a key role for GSK-3ß, which results in up-regulation in tumor versus normal tissue samples and associated to poor prognosis in sarcoma patients. Following this evidence, we evaluated CHIR99021, a GSK-3 inhibitor, as a potential drug for use in ES therapy. Our data highlight that, in ES cells, CHIR99021 induces cell cycle arrest, mitotic catastrophe (MC) and autophagic response, resulting in reduced cell proliferation. Our results support the potential efficacy of CHIR99021 in ES treatment and encourage further preclinical and clinical studies.


Assuntos
Autofagia/efeitos dos fármacos , Mitose/efeitos dos fármacos , Piridinas/farmacologia , Pirimidinas/farmacologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/fisiologia , Humanos , Moduladores de Mitose/farmacologia , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Análise de Sobrevida
3.
Oncologist ; 25(6): e928-e935, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31943506

RESUMO

BACKGROUND: Although American Society of Clinical Oncology and European Society for Medical Oncology guidelines have identified the negative prognostic factors that clinicians have to consider when treating their patients with stage II colon cancer (CC), the role of histological subtype is controversial. SUBJECTS, MATERIALS, AND METHODS: The randomized, multicenter, phase III TOSCA trial compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. The objective of this substudy was to evaluate the influence of histological subtypes on the impact of the treatment duration of adjuvant chemotherapy in terms of relapse-free survival (RFS) and overall survival (OS) in 85 mucinous adenocarcinoma (MUC) and 389 nonmucinous adenocarcinoma (NMUC) patients with high-risk stage II, grade 3 CC. RESULTS: A significant interaction between treatment duration and histology was observed in both RFS (p = .027) and OS (p = .017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03-15.17; p = .045) and OS (HR, 9.56; 95% CI, 1.14-79.98; p = .037) were detected for patients treated in the 3-month arm. No statistically significant differences were found in the subgroup of patients with NMUC. CONCLUSION: Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to assess the combined use of histology and other prognostic/predictive factors to define the administration of chemotherapy in patients with stage II CC and to improve their prognosis. IMPLICATIONS FOR PRACTICE: Although ASCO and ESMO guidelines define the prognostic factors for patients with stage II colon cancer to establish the use of adjuvant chemotherapy, the influence of histological subtypes is controversial in this population. This study underscores that patients with grade 3 mucinous adenocarcinomas may need adjuvant chemotherapy with oxaliplatin and fluoropyrimidines for a duration of 6 months rather than 3 months.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Prognóstico
4.
Heliyon ; 10(11): e31949, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882375

RESUMO

The present case report is aimed to highlight the difficulty and the reason for the delayed diagnosis of phosphaturic mesenchymal tumors, emphasizing the need of standardized protocols for diagnosis, surgery and follow-up in high-volume hospitals. The clinical signs and symptoms, diagnostic and therapeutic procedures, immunohistological features were analyzed. Delayed diagnosis of phosphaturic mesenchymal tumor was primarily due to non-specific clinical symptoms such as fatigue, muscular and bone pain, and multiple fractures. This cryptic clinical picture made the diagnosis tricky that led to treatment of patient for non-specific pain and stress fractures before to consider the tumor-induced osteomalacia syndrome. Some well-documented studies were found in the literature in which the history of trauma is a critical trigger of glomus tumors. Extra-subungual tumors most frequently occur in the knee and ankle regions, particularly among young adults, and the diagnosis is typically made approximately 7.2 years after initial symptom onset. The difficult tumor localization represented an additional obstacle to the prompt treatment, leading to delayed curative surgery.

5.
Diseases ; 12(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38534971

RESUMO

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for "extended" anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines plus panitumumab regimen, he suffered a massive right coronary artery (RCA) thrombosis. Another patient with no cardiovascular (CV) risk factors and affected by advanced bladder cancer was treated with a platinum-containing regimen and suffered an acute inferior myocardial infarction 2 days after chemotherapy administration. He was successfully treated with primary Percutaneous Transluminal Coronary Angioplasty of RCA, discontinuing platinum-based therapy. Our observations raise the issue of cancer-associated thrombosis (CAT) complexity and the potential correlation between arterial and venous thrombotic events. Moreover, physicians should be aware of the thrombotic risk associated with anticancer therapies, suggesting that an appropriate prophylaxis should be considered.

6.
Future Oncol ; 9(1): 127-33, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23252570

RESUMO

Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor. Our experience confirms that inhibition of angiogenic factors to treat cancer is a novel challenge for the oncologist and requires the cardiologist's support.


Assuntos
Indutores da Angiogênese/metabolismo , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Indóis/efeitos adversos , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/metabolismo , Pirróis/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Adulto , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Evolução Fatal , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Indóis/administração & dosagem , Indóis/uso terapêutico , Pessoa de Meia-Idade , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Pirróis/administração & dosagem , Pirróis/uso terapêutico , Sunitinibe , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/tratamento farmacológico
7.
Front Oncol ; 12: 986123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249019

RESUMO

Background and objective: The oncogenic effect of ionizing radiation is widely known. Sarcomas developing after radiation therapy (RT), termed "iatrogenic disease of success", represent a growing problem, since the advancements in cancer management and screening programs have increased the number of long-term cancer survivors. Although many patients have been treated with radiation therapy, only few data are available on radiation-induced sarcomas (RIS). Methods: We examined the medical and radiological records of 186 patients with histologically proven soft tissue and bone sarcomas, which referred to IRCCS CROB Centro di Riferimento Oncologico della Basilicata from January 2009 to May 2022. Among them, seven patients received a histological diagnosis of secondary RIS, according to Cahan's criteria. Clinicopathological features and treatment follow-up data of RIS patients were retrospectively analyzed. Results: Among these secondary RIS, five arose in irradiated breast cancer (5/2,570, 0.19%) and two in irradiated head and neck cancer (2/1,986, 0.10%) patients, with a mean onset latency time of 7.3 years. The histology of RIS was one desmoid tumor, two angiosarcomas, one chondrosarcoma, two leiomyosarcomas, and one undifferentiated pleomorphic sarcoma. Out of the seven RIS, one received radiotherapy, one received electrochemotherapy (ECT), one received a second-line chemotherapy, three were subjected to three lines of chemotherapy, and one underwent radiofrequency ablation, chemotherapy, and ECT. Median survival time is 36 months. No significant survival differences were found stratifying patients for age at RT, latency time, and age at RIS diagnosis. Conclusions: RIS represents a possible complication for long-survivor cancer patients. Therefore, adherence to a strict follow-up after the radiation treatment is recommended to allow early diagnosis and optimal management of RIS patients. After the planned follow-up period, considering the long-term risk to develop a RIS, a specific multispecialty survivorship care plan could be of benefit for patients.

8.
Ann Ital Chir ; 91: 605-610, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33554950

RESUMO

BACKGROUND: In our surgical daily activity, we report the observation of rare tumour as Gastrointestinal Stromal Tumours (GIST). We report the incidence and behaviour of new cases of GIST operated in our Center during the last decade, from 2008 to 2018 and here we also describe the concomitant observation of a second gastroenteric tumor. METHOD: We have examined all the case files and histological examinations of patients with CD 117-positive GISTs treated in our Institute from 2008 to 2018. We have gathered data regarding clinical symptoms at the time of diagnosis, tumour site, type of surgery performed, tumour size, histopathological data and follow up data. RESULTS: We have analysed 950 cases of patients who underwent surgery for gastrointestinal neoplasia in our department from 2008 to 2018. We have found 12 cases affected by GIST and in 4 cases it was also a second tumour. In two cases GIST were incidentalomas and in the others two patients a second tumour was incidentally observed in primary GIST. CONCLUSION: Patients with GIST run the risk of developing a second neoplasm, nearly twice as high as the general population with a negative impact on survival; also, incidental GIST is often observed requiring a better molecular characterization for the high risk of developing second neoplasms with the aim of achieving an early diagnosis. KEY WORDS: Gist, Second neoplasm, Surgery.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Segunda Neoplasia Primária , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/epidemiologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/cirurgia
9.
ESMO Open ; 2(4): e000229, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29018575

RESUMO

BACKGROUND: TAS-102 improves overall survival (OS) in patients with metastatic colorectal cancer (mCRC) refractory to standard treatments. However, predictive biomarkers of efficacy are currently lacking. PATIENTS AND METHODS: We treated a cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single institution expanded access, compassionate use programme. We stratified patients in two groups according to number of cycles received (<6 cycles and ≥6 cycles). OS, progression-free survival (PFS) and safety were evaluated. RESULTS: Thirteen out of 43 patients (30%) obtained a clinically relevant disease control with TAS-102 therapy. Eleven of them were treated for ≥6 cycles with TAS-102, reaching a median PFS of 7.5 months (95% CI 5.8 to 9.2 months) and a median OS of 11.2 months (95% CI range not reached yet). A trend towards significance (p=0.08) between a good performance status and response to TAS-102 was observed. Further, 7 out of the 11 TAS-102 long-treated patients achieved a clinical benefit from a previous treatment with regorafenib. A significant correlation between regorafenib and TAS-102 clinical efficacy was observed (p=0.008). Six out 13 regorafenib-naïve patients were treated with regorafenib after progression from TAS-102. All these patients achieved SD with a median duration of treatment with regorafenib of 6.1 months (range, 1.6-6.7). CONCLUSION: Patients with mCRC in good clinical conditions, even though having been heavily pretreated with all the available treatment options, could obtain a significant clinical benefit from treatment with TAS-102. Moreover, a previous clinical benefit obtained with regorafenib is potentially predictive of clinical efficacy of subsequent TAS-102 treatment.

10.
Oncology ; 71(5-6): 341-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17855795

RESUMO

OBJECTIVE: Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting. METHODS: 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Taxoides/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Cisplatino/efeitos adversos , Diarreia/induzido quimicamente , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Estudos de Viabilidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Neutropenia/induzido quimicamente , Estudos Prospectivos , Taxa de Sobrevida , Taxoides/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
11.
J Clin Oncol ; 29(20): 2773-80, 2011 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-21606427

RESUMO

PURPOSE: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. PATIENTS AND METHODS: Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m(2)/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m(2) weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. RESULTS: Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). CONCLUSION: Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fracionamento da Dose de Radiação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Itália , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Análise de Sobrevida
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