GH and IGF System: The Regulatory Role of miRNAs and lncRNAs in Cancer

Growth hormone (GH) and the insulin-like growth factor (IGF) system are involved in many biological processes and have growth-promoting actions regulating cell proliferation, differentiation, apoptosis and angiogenesis. A recent chapter in epigenetics is represented by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) which regulate gene expression. Dysregulated miRNAs and lncRNAs have been associated with several diseases including cancer. Herein we report the most recent findings concerning miRNAs and lncRNAs regulating GH and the IGF system in the context of pituitary adenomas, osteosarcoma and colorectal cancer, shedding light on new possible therapeutic targets. Pituitary adenomas are increasingly common intracranial tumors and somatotroph adenomas determine supra-physiological GH secretion and cause acromegaly. Osteosarcoma is the most frequent bone tumor in children and adolescents and was reported in adults who were treated with GH in childhood. Colorectal cancer is the third cancer in the world and has a higher prevalence in acromegalic patients

Endometrial carcinoma: Past, present, and future

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Modulation of micrornome by human cytomegalovirus and human herpesvirus 6 infection in human dermal fibroblasts: Possible significance in the induction of fibrosis in systemic sclerosis

Human cytomegalovirus (HCMV) and Human herpesvirus 6 (HHV‐6) have been report-edly suggested as triggers of the onset and/or progression of systemic sclerosis (SSc), a severe autoimmune disorder characterized by multi‐organ fibrosis. The etiology and pathogenesis of SSc are still largely unknown but virological and immunological observations support a role for these beta-herpesviruses, and we recently observed a direct impact of HCMV and HHV‐6 infection on the expression of cell factors associated with fibrosis at the cell level. Since miRNA expression has been found profoundly deregulated at the tissue level, here we aimed to investigate the impact on cell microRNome (miRNome) of HCMV and HHV‐6 infection in in vitro infected primary human dermal fibroblasts, which represent one of the main SSc target cells. The analysis, performed by Taq-man arrays detecting and quantifying 754 microRNAs (miRNAs), showed that both herpesviruses significantly modulated miRNA expression in infected cells, with evident early and late effects and deep modulation (>10 fold) of >40 miRNAs at each time post infection, including those previously recognized for their key function in fibrosis. The correlation between these in vitro results with in vivo observations is strongly suggestive of a role of HCMV and/or HHV‐6 in the multistep patho-genesis of fibrosis in SSc and in the induction of fibrosis‐signaling pathways finally leading to tissue fibrosis. The identification of specific miRNAs may open the way to their use as biomarkers for SSc diagnosis, assessment of disease progression and possible antifibrotic therapies

Role of circulating mirnas in therapeutic response in epithelial ovarian cancer: A systematic revision

Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence

Radiomics and artificial intelligence in malignant uterine body cancers: Protocol for a systematic review

IntroductionUterine body cancers (UBC) are represented by endometrial carcinoma (EC) and uterine sarcoma (USa). The clinical management of both is hindered by the complex classification of patients into risk classes. This problem could be simplified through the development of predictive models aimed at treatment tailoring based on tumor and patient characteristics. In this context, radiomics represents a method of extracting quantitative data from images in order to non-invasively acquire tumor biological and genetic information and to predict response to treatments and prognosis. Furthermore, artificial intelligence (AI) methods are an emerging field of translational research, with the aim of managing the amount of data provided by the various -omics, including radiomics, through the process of machine learning, in order to promote precision medicine.ObjectiveThe aim of this protocol for systematic review is to provide an overview of radiomics and AI studies on UBCs.Methods and analysisA systematic review will be conducted using PubMed, Scopus, and the Cochrane Library to collect papers analyzing the impact of radiomics and AI on UBCs diagnosis, prognostic classification, and clinical outcomes. The PICO strategy will be used to formulate the research questions: What is the impact of radiomics and AI on UBCs on diagnosis, prognosis, and clinical results? How could radiomics or AI improve the differential diagnosis between sarcoma and fibroids? Does Radiomics or AI have a predictive role on UBCs response to treatments? Three authors will independently screen articles at title and abstract level based on the eligibility criteria. The risk of bias and quality of the cohort studies, case series, and case reports will be based on the QUADAS 2 quality assessment tools

Emerging Role of MicroRNAs in the Therapeutic Response in Cervical Cancer: A Systematic Review

Cervical cancer is a common female cancer, with nearly 600,000 cases and more than 300,000 deaths worldwide every year. From a clinical point of view, surgery plays a key role in early cancer management, whereas advanced stages are treated with chemotherapy and/or radiation as adjuvant therapies. Nevertheless, predicting the degree of cancer response to chemotherapy or radiation therapy at diagnosis in order to personalize the clinical approach represents the biggest challenge in locally advanced cancers. The feasibility of such predictive models has been repeatedly assessed using histopathological factors, imaging and nuclear methods, tissue and fluid scans, however with poor results. In this context, the identification of novel potential biomarkers remains an unmet clinical need, and microRNAs (miRNAs) represent an interesting opportunity. With this in mind, the aim of this systematic review was to map the current literature on tumor and circulating miRNAs identified as significantly associated with the therapeutic response in cervical cancer; finally, a perspective point of view sheds light on the challenges ahead in this tumor

Quality of life with vulvar carcinoma treated with palliative electrochemotherapy: The elechtra (electrochemotherapy vulvar cancer) study

The ELECHTRA (ELEctroChemoTherapy vulvaR cAncer) project was conceived to collect data on palliative electrochemotherapy (ECT) in vulvar cancer (VC) assessing patients’ outcomes (response and survival) and impact on quality of life (QoL). After reporting outcome data in 2019, here, we present the results on QoL. A multicenter prospective observational study was conducted on patients with VC refractory or not amenable to standard therapies undergoing palliative ECT as per clinical practice. The following questionnaires were administered before and after ECT (two and four months later, early and late follow-up): visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy—Vulva cancer (FACT—V). Analyses were conducted on both the whole study population and by subgroups (clinical response after ECT and site, number and size of lesions). Questionnaires from 55 patients were evaluated. Compared to the baseline (6.1 ± 2.1), the VAS was significantly reduced at early (4.3 ± 2.5) and late follow-up (4.6 ± 2.8) (p < 0.0001). The FACT—V score improved significantly at early (9.6 ± 4.0) (p < 0.0001) and late follow-up (8.9 ± 4.1) (p < 0.0054) as compared to the baseline (7.1 ± 3.6). No EQ-5D-5L statistically significant changes were observed. Subgroup analyses showed worse QoL in patients with stable or progressive disease, posterior site and multiple or larger than 3 cm nodules. This is the first study reporting improved QoL in VC patients after palliative ECT. Based on these results, ECT in VC should be considered an effective option based on the favorable outcomes both in terms of response and QoL

Can miRNAs be useful biomarkers in improving prognostic stratification in endometrial cancer patients? An update review

Endometrial cancer (EC) is the most common gynecological cancer, with annual incidence rates in Western countries ranging between 15 and 25 per 100 000 women. About 15% to 20% of patients with EC have high-risk disease and follow an aggressive clinical course. Unfortunately, the assessment of histologic parameters is poorly reproducible and conventional clinicopathological and molecular features do not reliably predict either the patient's response to the available treatments or the definition of personalized therapeutic approaches. In this context, the identification of novel diagnostic and prognostic biomarkers, which can be integrated in the current classification schemes, represents an unmet clinical need and an important challenge. miRNAs are key players in cancer by regulating the expression of specific target genes. Their role in EC, in association with clinical and prognostic tumor biomarkers, has been investigated but, so far, with little consensus among the studies. The present review aims to describe the recent advances in miRNAs research in EC taking into consideration the current classification schemes and to highlight the most promising miRNAs. Finally, a perspective point of view sheds light on the challenges ahead in the landscape of EC

Malignant Bowel Obstruction in Ovarian Cancer Recurrence: The Role of Palliative Surgery in a Decision-Making Process

Background: Malignant bowel obstruction (MBO) is often the latest stage in ovarian cancer (OC). The therapy of this condition ranges from medical waiting to surgery. The objective of this pilot study is to compare the two strategies so that we can provide a path forward for future studies. Methods: From 700 women diagnosed with OC in the database of the Division of Gynecologic Oncology we crossed the names of those admitted by the emergency services of the IRCSS Azienda Ospedaliero Universitaria of Bologna, Italy. We selected MBO patients with a history of OC as the only neoplastic condition and compared the results between medical conduct and surgery to restore intestinal transit. Results: Of the 700 women in our database, 36 were eligible for study according to the inclusion and exclusion criteria: 9 in surgery group and 27 in medical group. Surgical conduct (tumor biopsy and stoma) appears to be resolutory for the obstruction and have a better result than medical therapy regarding recurrence of MBO, despite the development of greater complications. Relapses of MBOs occurred in 11% of surgical patients and 44% of medical patients (p = 0.0714). Furthermore, after surgical treatment, five patients (55%) experienced postoperative complications; in four cases, severe anemia requiring blood transfusion, while one patient developed post-surgical sepsis, which evolved into multiple organ failure and death. Of the 9 patients treated surgically, 2 (22%) were given surgery as a first choice. In most cases (78%), surgery was decided upon when medical treatment failed. The only discriminative factor appears to be age. The length of hospitalization increased with the patient’s age (p = 0.0181) as statistically significant factors for a worse outcome in surgery. Conclusions: MBO requires complex and multidisciplinary management where different factors need to be considered before initiating surgical therapy. Future studies are needed to deal with this complex problem