Search

NC-6004 is a nanoparticle developed using micellar technology that can improve release of cisplatin, a standard treatment for many cancer types, and achieve selective distribution to tumors. Here, in the Phase II portion of this study, the activity, safety, tolerability, and effects on quality of life of NC-6004 in combination with gemcitabine was examined in 34 squamous non-small cell lung carcinoma (NSCLC) patients, 50 biliary tract cancer patients, and 13 bladder cancer patients. All patients received 135 mg/m2 NC-6004 on day one and 1,250 mg/m2 gemcitabine on days one and eight. The median progression-free survival was 3.9 months in NSCLC patients, 4.3 months in biliary tract cancer patients, and 6.8 months in bladder cancer patients fit for cisplatin treatment. The most frequently reported Grade 3 Treatment Emergent Adverse Events across all cohorts were nausea, anemia and neutropenia, and hyponatremia. Quality of life measures for patients who received the combined therapy were generally consistent with expectations for patients undergoing chemotherapy. Overall, combined NC-6004 and gemcitabine treatment resulted in long-lasting antitumor activity and had a favorable safety profile, suggesting that it should be investigated further as a therapy for various types of cancer.

Although neuroendocrine tumours (NETs) are intensively studied, their diagnosis and consequently personalised therapy management is still puzzling due to their tumoral heterogeneity. In their theragnosis algorithm, receptor somatostatin scintigraphy takes the central place, the diagnosis receptor somatostatin analogue (RSA) choice depending on laboratory experience and accessibility. However, in all cases, the results depend decisively on correct radiotracer tumoral uptake quantification, where unfortunately there are still unrevealed clues and lack of standardization. We propose an improved method to quantify the biodistribution of gamma-emitting RSA, using tissular corrected uptake indices. We conducted a bi-centric retrospective study on 101 patients with different types of NETs. Three uptake indices obtained after applying new corrections to areas of interest drawn for the tumour and for three reference organs (liver, spleen and lung) were statistically analysed. For the corrected pathological uptake indices, the results showed a significant decrease in the error of estimating the occurrence of errors and an increase in the diagnostic predictive power for NETs, especially in the case of lung-referring corrected index. In conclusion, these results support the importance of corrected uptake indices use in the analysis of 99mTcRSA biodistribution for a better personalised diagnostic accuracy of NETs patients.

Colorectal cancer is a major cause of cancer-related death worldwide and is correlated with genetic and epigenetic alterations in the colonic epithelium. Genetic changes play a major role in the pathophysiology of colorectal cancer through the development of gene mutations, but recent research has shown an important role for epigenetic alterations. In this review, we try to describe the current knowledge about epigenetic alterations, including DNA methylation and histone modifications, as well as the role of non-coding RNAs as epigenetic regulators and the prognostic and predictive biomarkers in metastatic colorectal disease that can allow increases in the effectiveness of treatments. Additionally, the intestinal microbiota’s composition can be an important biomarker for the response to strategies based on the immunotherapy of CRC. The identification of biomarkers in mCRC can be enhanced by developing artificial intelligence programs. We present the actual models that implement AI technology as a bridge connecting ncRNAs with tumors and conducted some experiments to improve the quality of the model used as well as the speed of the model that provides answers to users. In order to carry out this task, we implemented six algorithms: the naive Bayes classifier, the random forest classifier, the decision tree classifier, gradient boosted trees, logistic regression and SVM.

Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation burden. Monoclonal antibodies that block immune checkpoints can induce long-term durable responses in some patients. Pembrolizumab is the first checkpoint inhibitor approved in the EU to treat dMMR–MSI-H metastatic CRC. Materials and Methods: Our study assesses the regional variability of MSI-H colorectal cancer tumors in Romania. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks containing tumor samples from 90 patients diagnosed with colorectal cancer were collected from two tertiary referral Oncology Centers from Romania. Tissues were examined for the expression loss of MMR proteins (MLH1, PMS2, MSH2, MSH6) using immunohistochemistry or MSI status using polymerase chain reaction (PCR), respectively. Results: MSI-H was detected in 19 (21.1%) patients. MSI-H was located more in ascending colon (36.8% vs. 9.9%, p-value = 0.0039) and less in sigmoid (5.3% vs. 33.8%, p-value = 0.0136) than MSS patients. Most patients were stage II for MSI-H (42.1%) as well as for MSS (56.3%), with significant more G1 (40.9% vs. 15.8%, p-value = 0.0427) for MSS patients. Gender, N stage, and M stage were identified as significant prognostic factors in multivariate analysis. MSI status was not a statistically significant predictor neither in univariate analysis nor multivariate analysis. Conclusion: Considering the efficacy of PD-1 inhibitor in metastatic CRC with MSI-H or dMMR, and its recent approval in EU, it is increasingly important to understand the prevalence across tumor stage, histology, and demographics, since our study displayed higher regional MSI-H prevalence (21%) compared to the literature.

Noncoding RNAs (ncRNAs) include a diverse range of RNA species, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs, ncRNAs of approximately 19–25 nucleotides in length, are involved in gene expression regulation either via degradation or silencing of the messenger RNAs (mRNAs) and have roles in multiple biological processes, including cell proliferation, differentiation, migration, angiogenesis, and apoptosis. LncRNAs, which are longer than 200 nucleotides, comprise one of the largest and most heterogeneous RNA families. LncRNAs can activate or repress gene expression through various mechanisms, acting alone or in combination with miRNAs and other molecules as part of various pathways. Until recently, most research has focused on individual lncRNA and miRNA functions as regulators, and there is limited available data on ncRNA interactions relating to the tumor growth, metastasis, and therapy of cancer, acting either on mRNA alone or as competing endogenous RNA (ceRNA) networks. Triple-negative breast cancer (TNBC) represents approximately 10%–20% of all breast cancers (BCs) and is highly heterogenous and more aggressive than other types of BC, for which current targeted treatment options include hormonotherapy, PARP inhibitors, and immunotherapy; however, no targeted therapies for TNBC are available, partly because of a lack of predictive biomarkers. With advances in proteomics, new evidence has emerged demonstrating the implications of dysregulation of ncRNAs in TNBC etiology. Here, we review the roles of lncRNAs and miRNAs implicated in TNBC, including their interactions and regulatory networks. Our synthesis provides insight into the mechanisms involved in TNBC progression and has potential to aid the discovery of new diagnostic and therapeutic strategies.

The aim of this study is to evaluate the periodontal status parameters in patients treated with chemotherapy, with or without the adjuvant bevacizumab, to establish a correlation between the type of administered chemotherapy and periodontal status.

Metastatic or advanced breast cancer (mBC/ABC) remains incurable despite many different systemic treatment options. Hormone receptor positive (HR+) disease represents the most common subtype in both early and advanced disease. A better understanding of the biology of this BC subtype, in particular regarding potential mechanisms of endocrine resistance, has led to the development of CDK4/6 inhibitors. All three selective CDK4/6 inhibitors, palbociclib, ribociclib and abemaciclib have shown to significantly improve progression-free survival (PFS) when combined to endocrine therapy as first-line treatment for patients with HR+/HER-2 negative ABC, who have progressed on or after adjuvant endocrine therapy. All three of them have also shown an improved PFS as 2nd line therapy for HR+/Her2 negative ABC. Their toxicity profile is favorable, with hematological toxicity (mainly neutropenia) being predominant, followed by diarrhea and fatigue. Quality of life has been maintained in the 1st line setting or improved in the 2nd line setting. Overall survival (OS) has been reported so far only in 2 out of 7 trials as first line therapy and the difference did not reach statistical significance. In this article we review the biology of CDK signaling pathway and its inhibitors, preclinical and clinical data of all three investigated selective CDK4/6 inhibitors and their toxicity. We also discuss how these agents are being included in current international guidelines and future directions for these agents in other subtypes of breast cancer, in both advanced disease and early-stage disease.

Advanced breast cancer (ABC), also called metastatic or secondary breast cancer, is a treatable but still generally incurable condition, although important advances have been made in our understanding and management of this disease.

Hepatic arterial infusion (HAI) was evaluated for different drugs to treat hepatic metastasis from colorectal cancer (CRC). Combination treatment with 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) is effective for CRC. A phase II study was conducted to evaluate concomitant HAI administration of oxaliplatin and intravenous leucovorin, 5-FU and irinotecan (FOLFIRI) for patients with inoperable liver metastasis, which had chemotherapy with oxaliplatin (OX) 85 mg/m(2) HAI plus systemic intravenous chemotherapy [leucovorin 200 mg/m(2), 5-FU 2400 mg/m(2) and irinotecan (IRI) 160 mg/m(2) in 48 hours]. We treated 24 patients. Neutropaenia was the most frequent toxicity. The main HAI-related toxicity was pain. Two patients (8%) obtained complete response and 17 patients (70%) partial response, giving an objective response rate of 78%. Median follow-up was 22.8 months, and median overall and disease-free survival times were 29 and 20 months, respectively. Therefore, OX HAI and intravenous FOLFIRI is feasible and effective in patients with metastatic CRC.