Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have ...a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1–negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01–7.76). Moreover, membrane hENT-1–positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.
•Human equilibrative nucleoside transporter 1 (hENT-1) regulates intrahepatic cholangiocarcinoma (iCC) growth.•The mechanism relies on hENT-1 localisation on tumour cell membrane.•Membrane hENT-1 positive patients have higher Ki67-positive tumour cells and worse survival than membrane hENT-1 negative.
GARAJOVÁ I., NEPOTI G., PARAGONA M., BRANDI G. & BIASCO G. (2013) European Journal of Cancer Care22, 125–132
Port‐a‐Cath‐related complications in 252 patients with solid tissue tumours and the first ...report of heparin‐induced delayed hypersensitivity after Port‐a‐Cath heparinisation
The use of the subcutaneous Port‐a‐Catheters (Port‐a‐Caths) provides an important mean of venous access for oncological patients. The aim of our retrospective consecutive single‐centre study was to investigate Port‐a‐Cath‐related complications in 252 cancer patients. Overall period of Port‐a‐Caths maintenance was 25 months. The strategy of our centre is to keep Port‐a‐Caths in situ up to the end of follow‐up in adjuvant cancer patients. A total of 22 complications were recorded (8.73%). Interventional complications occurred in four patients. The main complications during Port‐a‐Cath use included thrombosis (4 patients, 1.58%), infections (4 patients, 1.58%), persistent pain or discomfort (3 patients, 1.19%) and dislocations (2 patients, 0.79%). Median time to the occurrence of any type of complications was 4.5 months. Eleven Port‐a‐Caths were removed due to complications (4.36%). Similar rate of Port‐a‐Cath‐related thrombosis/infection was seen in adjuvant and advanced cancer patients (no statistical significance). Continuous infusion of anticancer therapy via a Port‐a‐Cath system is a relatively safe procedure, although major complications might occur. We are first to describe heparin‐induced delayed hypersensitivity after heparinisation of Port‐a‐Cath. This fact should influence the preference to keep the Port‐a‐Cath after completion of adjuvant anticancer treatment.
Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety ...profile, dose intensity, and activity of different chemotherapy regimens in this setting.
gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed.
A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS.
Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.
•Nab-paclitaxel plus gemcitabine dose intensity and toxicity were as expected from the literature.•Toxicity with platinum-based triplets was unmodified to the price of consistently reduced dose intensity.•Dose intensity for platinum-based quadruplets was preserved to the price of greater hematological toxicity and diarrhea.•RECIST and CA19.9 responses were higher with platinum-based triplets and quadruplets in metastatic patients.•Longer progression-free and overall survival were observed with platinum-based three- and four-drug regimens in stage IV (AJCC/UICC TNM 8th Edition, 2017) patients.
Colorectal cancer (CRC) is one of the most frequent malignant diseases in the world. Metastatic spread of the cancer to the lymph nodes is a crucial factor for progression and therapeutic management ...of the disease. We analysed gene expression profiles of CRC patiens by low-density cancer-focused oligonucleotide microarrays to identify new predictive markers of the extent of the disease and for better understanding of CRC progression. Relative expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 20 tumor samples. Statistical analysis of gene expression data identified 3 genes (HSP110, HYOU1 and TCTP) significantly up-regulated in primary tumors of patients who developed lymph node metastasis. We have shown, for the first time, that up-regulation HSP110 and HYOU1 expression is associated with lymph node involvement in CRC. We validated the differences in HSP110 expression in an independent group of 30 patients of all clinical stages by real-time PCR. We identified significant up-regulation of HSP110 expression in colorectal tumors compared to adjacent non-tumoral tissue (p<0.0003). We observed significant differences of HSP110 gene expression between metastatic and localized disease (p=0.031) and negative trend of HSP110 gene expression and overall survival of CRC patients. We suggest that HSP110 gene is a promising molecular predictor in CRC.
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