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Background: Alteration of the expression of human epidermal growth factor receptor-2 gene as an oncogenic pathway in breast cancer was first explored in the 1980'. Since then, tremendous progress has been made in treating HER2-positive breast cancer. Methods: We performed a narrative type review of the existing literature using as a starting point the PubMed database, investigated by keywords, later the search being refined and the articles that we considered relevant were selected. The approach to the topic under discussion being variable in the various studies identified convinced us of the inappropriateness of a meta-analysis. As a secondary method of analysis, we evaluated the bibliography of each of the selected studies and from this we identified other publications of interest. Results: At present, there are three major classes of FDA-approved anti-HER2 agents: monoclonal antibodies (Trastuzumab, Pertuzumab and Margetuximab), TKIs (Lapatinib, Neratinib and Tucatinib) and antibody-drug conjugates (T-DM1 and T-DXd). The treatment of HER2+ breast cancer suffered some changes in the last few years. If in 2018, after progression under first-line treatment with taxane-trastuzumab/pertuzumab and second line with T-DM1 was a big challenge, being up to the oncologist to choose from lapatinib-capecitabine, trastuzumab-lapatinib or different chemotherapeutic agents, depending on toxicities and therapies available in the country, nowadays we have a new third- and fourth-line FDA approved standard, which consists of tucatinib-trastuzumab-capecitabine and trastuzumab-deruxtecan. Conclusion: Times are very exciting for HER2-positive disease. What differentiates novel therapies and if we do it better is both the question that we tried to give an answer to in this review of literature, but it remains at the same time a topic of discussion and a directive for analysis in the future, because we are only getting closer to an optimal version of treatment for HER2+ breast cancer, hoping that the introduction of new drugs and the establishment of new indications for old drugs will allow us to standardize the treatment of these patients.

This study aimed to create a generic profile of patients with NETs and to establish the prioritization criteria for somatostatin receptors scintigraphy (SRS), within the NETs diagnostic algorithm, being the first study of this kind conducted in Romania. Material and methods: A bi-centric, retro-prospective study comprising 103 patients with NETs, evaluated through 99mTc-TOC SRS, in two nuclear medicine departments from “Sf. Spiridon” County Clinical Emergency Hospital Iasi, Romania and Center of Nuclear Medicine, University Clinical Center of Kragujevac, Serbia. We analyzed the clinical-paraclinical features of included patients, as a starting point for streamlining the selection of patients for SRS. Results and discussion: The total group of patients included 47.57 % men and 52.43 % women, the age varying between 21-83 years. The most frequent primary NETs were represented by pNETs, and GI-NETs and the symptoms were nonspecific for majority of analyzed patients. Both prospective and retrospective analysis showed that SRS was followed by positive results. For prospectively analyzed patients, due to the used customized sheets, it was extremely easy to identify four SRS prioritization criteria. Conclusions: This study could outline the profile of patients with NETs, as the starting point for streamlining patient selection for SRS. The four prioritization criteria proposed by us could guide the diagnostic algorithm.

Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy’s efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed.

The practice of oncology continues to be an area of continuous renewal. The volume of knowledge in the field of cancer therapy is increasing rapidly compared to any other medical discipline, constraining the need for permanent information. The first data on malignancies are linked to the 11th century BC. The concerns of physicians were attracted to the cancerous disease, the observations and hypotheses regarding it being mentioned in different writings of the time. The increased frequency of cancer in the oro-maxillofacial region is favored by a number of factors: the great diversity of maxillofacial structures and the very important changes in the phylogenesis and ontogeny of these structures; the embryonic existence of the branchial arches, with the possibility of remaining residues in this stage; function of the intense quality of the face region and the oral region, as the first segment of the matter import apparatus; the multitude of irritant factors, which play an important role in the occurrence of cancer ( temperature, food hardness, dust, chemical noxiousness). The improvement of the methods and techniques of the surgical operations performed on the maxillofacial region had a decisive influence on the treatment of this region. In patients whose pathologic (bleeding diathesis, heart disease, liver disease, diabetes, etc.) can lead to various complications (local and general), interventions of oral and maxillofacial surgerycan perform as a preparation prior appropriate. The study includes a sample of 48 patients with malignant tumors of the salivary glands. The treatment of malignant tumors of the salivary gland have to be as wide early and surgically, with radiotherapy and / or multi-agent chemotherapy. Radiotherapy alone is insufficient, indicated only as palliative treatment.

The Primitive Gastric Lymphoma represents the extra-ganglionic non-Hodgkin lymphoma most frequently and comprises a large spectrum, ranging from the mucosa-associated lymphoid tissue (MALT) lymphoma to aggressive diffuse large B-cell lymphoma. The Primitive Gastric Lymphoma is a rare tumor, with an occurrence ranging from 4% to 20% of non-Hodgkin lymphomas and approximatively 5% of primary gastric neoplasms. The chronic gastritis secondary to the infection with Helicobacter pylori was considered a major predisposing factor for MALT lymphoma. The clinical evolution and the prognosis of this disease depend on the subtype and histopathological stage at the moment of the diagnosis. Due to its rarity, many aspects of this neoplasm remain still controversial.

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.

Cancer immunotherapy has shifted the paradigm in cancer treatment in recent years. Immune checkpoint blockage (ICB), the active cancer vaccination and chimeric antigen receptor (CAR) for T-cell-based adoptive cell transfer represent the main developments, achieving a surprising increased survival in patients included in clinical trials. In spite of these results, the current state-of-the-art immunotherapy has its limitations in efficacy. The existence of an interdisciplinary interface involving current knowledge in biology, immunology, bioengineering and materials science represents important progress in increasing the effectiveness of immunotherapy in cancer. Cutaneous melanoma remains a difficult cancer to treat, in which immunotherapy is a major therapeutic option. In fact, enhancing immunotherapy is possible using sophisticated biomedical nanotechnology platforms of organic or inorganic materials or engineering various immune cells to enhance the immune system. In addition, biological devices have developed, changing the approach to and treatment results in melanoma. In this review, we present different modalities to modulate the immune system, as well as opportunities and challenges in melanoma treatment.

The outcome of colorectal cancer (CRC) can be improved by the identification of prognostic biomarkers. This systematic review of observational cohort and case-control studies was conducted to investigate the role of Endoglin (CD105) in the prognosis of CRC. The databases PubMed, Web of Science, Scopus, and Cochrane CENTRAL were searched to identify the qualified studies using the relevant keywords. After the removal of duplicate articles, the screening was implemented on the titles, abstracts, and potential full-text articles. Afterward, the eligible cohort and case-control studies were identified, and the data were extracted into an Excel datasheet. In total, 11 observational cohort studies and 1 case-control study were identified to be eligible for this systematic review. The majority of the included studies achieved a moderate to high-degree quality according to the Newcastle-Ottawa Scale. Moreover, the eligible studies included a total of 1,400 patients with CRC and mean age of 60 years, the majority of whom were male. Endoglin was observed to be more upregulated in colorectal carcinomas and associated with poor survival outcomes, compared to healthy controls. The levels of Endoglin seem to reflect the degree of cancer invasiveness, therefore predicting dismal prognosis in patients with CRC. Larger and well-designed clinical studies with longer follow-up intervals are needed to investigate the role of Endoglin and its association with cancer metastasis.

Cancer is the leading cause of mortality and morbidity worldwide. The side effects of cancer treatment affect the quality of life. Cancer patients search for antioxidant dietary supplements and natural products during or after conventional cancer treatment for the alleviation of side effects, improvement of the benefits of treatment, and promotion of well-being. However, the efficacy and safety of these products remain controversial; moreover, previous data do not support the standardized use of those alternative treatments in clinics. The current study reviewed the manuscripts reporting the administration of antioxidants and natural products during cancer treatment and revised preclinical and clinical studies on various types of cancer. Most of the positive results were obtained from experimental animal models; however, human clinical studies are discouraging in this regard. Therefore, further precise and distinguishable studies are required regarding antioxidant dietary supplementation. Future studies are also needed to clarify dietary supplements’ mechanism of action and pharmacokinetics in a suitable cancer patient population that will benefit the therapeutic regimens. Despite the popularity of dietary supplements, clinicians and patients should always consider their potential benefits and risks. Patients should discuss with their physician before taking any dietary antioxidant supplements or natural products.

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.

First described in 1998, apelin is one of the endogenous ligands of the apelinergic receptor. Since its discovery, its possible role in human physiology and disease has been intensively studied. Apelin is a native cardioprotective agent that the body synthesizes to create atheroprotective, antihypertensive, and regenerative effects in the body. By antagonizing the RAA system, apelin could play an important role in heart failure and hypertension. It is also involved in myocardial protection against ischemia/reperfusion injury, post-ischemic remodeling, and myocardial fibrosis. A small number of studies even suggest that serum apelin levels may be involved the development of life-threatening arrhythmias. All this information generated excitement about potential therapeutic effects in patients with heart failure and myocardial infarction. The therapeutic index of apelin is unknown but is anticipated to be favorable based on the small number of studies. In this review, we summarize the mechanisms by which apelin exerts its cardioprotective effects and its connection with the cardiorenal axis. Also, we report the potential therapeutic applications of synthetic and native regulated apelin. If larger studies can be performed, it is possible that apelin-mediated drug treatment may play a major role for a large number of patients worldwide in the future.

Gene therapy represents a promising method for treating genetic disorders or diseases consisting in the transfer of genetic material (DNA) to cells in order to substitute or to slow down the evolution of the defective gene in cells. Theoretical models to predict DNA release are difficult to build in the classical approach of continuous and differentiable physical quantities, due to the high number of interdependent phenomena that occur simultaneous. The article presents a theoretical model based on the fractal theory of motions in the form of Scale Relativity Theory to describe nonlinear behaviors in gene therapy. Correlations of the theoretical model with experimental data are also observed.

Colorectal cancer is the third most prevalent malignancy in Western countries and a major cause of death despite recent improvements in screening programs and early detection methods. In the last decade, a growing effort has been put into better understanding how the immune system interacts with cancer cells. Even if treatments with immune checkpoint inhibitors (anti-PD1, anti-PD-L1, anti-CTLA4) were proven effective for several cancer types, the benefit for colorectal cancer patients is still limited. However, a subset of patients with deficient mismatch repair (dMMR)/microsatellite-instability-high (MSI-H) metastatic colorectal cancer has been observed to have a prolonged benefit to immune checkpoint inhibitors. As a result, pembrolizumab and nivolumab +/− ipilimumab recently obtained the Food and Drug Administration approval. This review aims to highlight the body of knowledge on immunotherapy in the colorectal cancer setting, discussing the potential mechanisms of resistance and future strategies to extend its use.

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.

Advanced breast cancer (ABC) in young women is defined as diagnosis of ABC prior to age 40. The multitude of factors that make treating breast cancer in young women challenging in early breast cancer is further increased in the advanced setting. Current guideline recommendations are generally based on data generated from studies in postmenopausal patients, although in recent years there have been more and more trials accommodating and inclusive of younger women. Available guidelines and evidence suggest that age alone should not dictate treatment decisions; rather treatment should be driven by biology, clinical aspects, and patient preference, as for older patients. Much like in the early setting, in the advanced setting there are unique psychosocial, fertility, and genetic issues, made all the more difficult in the presence of endocrine-responsive disease which requires rendering the women postmenopausal usually indefinitely.

The prevalence of both cancer and end-stage renal disease is increasing. In addition, medical advances have meant increased survival rates for both diseases. Many chemotherapeutics are renally excreted, and conversely, renal insufficiency promotes a pro-neoplastic state, including genitourinary and other cancers. Dialysis prolongs life while increasing cancer risk. Proposed oncogenic mechanisms include immune dysfunction, chronic inflammation, changes in gut microbiota and stimulation of the renin–angiotensin system. This review summarizes current concepts in the relationship between cancer and renal insufficiency.

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.

Background and Aim: In metastatic colorectal cancer, in the last 10 years, hepatic arterial infusion (HAI) was proposed as an alternative using various chemotherapy agents. The insertion of a port-a-cath in the hepatic artery is needed and there are various methods to do that, from classical to interventional approach. Patients and Methods: Patients were selected with metastatic colorectal cancer with inoperable liver metastasis only and were treated with oxaliplatin HAI, combined with systemic intravenously chemotherapy. The port-a-cath insertion was done using the classical approach in the same surgical time with the subclavicular vein port insertion. Results: Thirty-two patients were treated. During our experience we did not encounter intra-operative complications. Among the immediate post-operative complications mainly consisted of metabolic complications (6.2%) and infection was the most common late complication (9.4%). In one case we removed the port-a-cath, thus the patient was not able to continue the treatment. Conclusion: When talking about the safety of the procedure, we didn’t find it to be more at risk for the patients compared to the literature. Even though the antibiotic prophylaxis is done regularly, the risk of infection remains, especially as a late complication.