Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue

Ammendola, Michele; Currò, Giuseppe; Laface, Carmelo; Zuccalà, Valeria; Méméo, Riccardo; Luposella, Francesco; Laforgia, Mariarita; Zizzo, Nicola; Zito, Alfredo; Loisi, Donato; Patruno, Rosa; Milella, Lucia; Ugenti, Ippazio; Porcelli, Mariangela; Navarra, Giuseppe; Gadaleta, Cosmo Damiano; Ranieri, Girolamo

doi:10.3390/cells10020444

Cited by 16 publications

(12 citation statements)

References 99 publications

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“…Pancreatic cancer (PC) is the fourth most common cause of cancer mortality, with a 5-year survival rate of only 8%, although it is considered a rare tumor [ 1 , 2 , 3 ]. Standard therapies are represented by radical surgery and adjuvant chemotherapy for the early stages, although 60–70% of patients present a relapse after 2 years [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review

Laface

Laforgia

Molinari

et al. 2022

Cancers

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Advanced pancreatic cancer (PC) has a very poor prognosis due to its chemoresistant nature. Nowadays, only a few therapeutic options are available for PC, and the most effective ones are characterized by low response rates (RRs), short progression-free survival and overall survival, and severe toxicity. To improve clinical results, small series studies have evaluated loco-regional chemotherapy as a treatment option for PC, demonstrating its dose-dependent sensitivity towards the tumor. In fact, pancreatic arterial infusion (PAI) chemotherapy allows higher local concentrations of chemotherapeutic agents, sparing healthy tissues with a lower rate of adverse events compared to systemic chemotherapy. This therapeutic approach has already been evaluated in different types of tumors, especially in primary and metastatic liver cancers, with favourable results. With regard to advanced PC, a few clinical studies have investigated the safety and efficacy of PAI with promising results, especially in terms of RRs compared to systemic chemotherapy. However, clear evidence about its efficacy has not been established yet nor have the underlying mechanisms leading to its success. In this review, we aim to summarize the literature data on the clinical approaches to pancreatic arterial drug administration in terms of techniques, drug pharmacokinetics, and clinical outcomes for advanced PC.

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Section: Introductionmentioning

confidence: 99%

Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review

Laface

Laforgia

Molinari

et al. 2022

Cancers

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“…This is due to two main aspects: first, the slender and sparse anatomical pancreatic vascularization, although angiogenic rebound has been demonstrated in PDAC ( 8 , 12 ); secondly, the abundant dense desmoplastic stromal tissue that characterizes the microenvironment of PDAC, which is a true barrier that is impenetrable to the drugs. Obtaining elevated concentrations of chemotherapeutic agents in the tumor microenvironment might be the prerequisite for the penetration of the drugs into the desmoplastic stromal cancer tissue, to finally arrive near to, and get into, the tumor cells ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report

et al. 2022

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Patients affected by pancreatic ductal adenocarcinoma (PDAC) have very poor prognosis, whereby at a follow-up of 5 years, the mortality rate is very similar to the incidence rate. Globally, around 10% of patients are amenable to radical surgery at the time of diagnosis, which represents the only chance of cure or long-term survival for these patients. Almost 40% of patients with PDAC show locally advanced pancreatic cancer (LAPC). LAPC is not a metastatic disease, although it is not amenable to radical surgery. For these patients, systemic induction chemotherapy with intravenous FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, oxaliplatin) regimen is administered, with the aim of conversion to surgery, although the conversion rate remains low, at approximately 10% to 15%. Pancreatic arterial chemotherapy has been explored to overcome the intrinsic tumor pancreatic resistance to systemic chemotherapy, where an intra-arterial port-a-cath is placed by means of interventional oncology techniques under angiographic guidance in the operating theater. Here, we treated a patient with an intra-arterially modified FOLFIRINOX regimen. Three courses were administered, and the patient experienced no adverse events. At the end of the third course, the patient rapidly developed lung failure due to nosocomial Legionella pneumophila infection, despite the impressive pathological tumor response shown in the autopsy report. This is a first and unique report that demonstrates that pancreatic intra-arterial FOLFIRINOX can be safe and efficacious. We believe that this preliminary result will be confirmed in the next patients to be enrolled and that it provides a glimmer of hope for patients with this lethal disease.

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“…In fact, the mutated or abnormal expression of tyrosine kinases is often found in different types of cancers such as HCC, playing a pivotal role in tumor growth [ 23 , 24 ]. Therefore, preclinical and clinical research have documented the efficacy of TKIs in the treatment of several cancers [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. With regard to HCC, the first TKI with proven efficacy was Sorafenib in 2007 [ 37 ].…”

Section: Targeted Therapiesmentioning

confidence: 99%

“…Experimental data demonstrated the pathogenetic role of angiogenesis in tumor growth [ 31 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. As regards HCC, several studies showed the overactivation of VEGF and VEGFR signaling [ 101 , 102 , 103 , 104 , 105 ].…”

Section: Targeted Therapiesmentioning

confidence: 99%

“…As regards HCC, several studies showed the overactivation of VEGF and VEGFR signaling [ 101 , 102 , 103 , 104 , 105 ]. In support of these data, it has been described as the treatment with TKIs targeting the VEGF signaling pathway via multikinase inhibition that leads to a therapeutic benefit, albeit of modest size [ 11 , 27 , 31 , 33 , 35 , 36 , 93 , 103 , 106 ]. Hence, there is a necessity to further investigate alternative pathways targeting VEGF inhibition and tumor angiogenesis.…”

Section: Targeted Therapiesmentioning

confidence: 99%

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Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities

Laface¹,

Fedele²,

Maselli³

et al. 2022

Cancers

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Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver, accounting for 90% of all recorded cases. HCC is the third most common cause of cancer-related death, with a 5-year survival rate of just 3%. In the advanced stages, systemic treatments allow doctors to obtain clinical benefits, although the prognosis remains very poor. In the past few decades, new molecular targeted therapies against receptor tyrosine kinases have been developed and clinically evaluated. Sorafenib was the first oral tyrosine kinase inhibitor (TKI) approved for the treatment of advanced HCC in 2007. Subsequently, other TKIs, including Cabozantinib, Regorafenib, Lenvatinib, and vascular endothelial growth factor receptor (VEGFR) inhibitors such as Ramucirumab and VEGF inhibitors such as Bevacizumab have been approved as first- or second-line treatments. More recently, the combination of immune checkpoint inhibitors and VEGF inhibitors (Atezolizumab plus Bevacizumab) have been analyzed and approved for the treatment of advanced HCC. On the basis of the poor prognoses and the meager benefits deriving from the available systemic therapies, research into new treatments is extremely necessary. In this review, we focus on the available systemic therapies for advanced HCC, with a look toward the future.

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Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue

Cited by 16 publications

References 99 publications

Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review

Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review

A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report

Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities

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