Genetic, epigenetic and micro-environmental markers as predictors of prognosis, response and resistance to chemotherapy, targeted agents and immunotherapy in resected squamous cell lung carcinoma (SQLC).

Differently from lung adenocarcinoma, effective targeted therapies for lung squamous-cell cancer (SQLC) are still missing, although a series of molecular pathways are constantly altered. In this regard, the prognostic and/or predictive impact of potential drivers needs to be elucidated, in order to create a global portrait of SQLC patients. Nowadays, one of the main emerging research strategies in cancer is centered on the study of the genome of exceptional responder and prognostic outlier patients. Adopting this idea, we retrospectively analysed a multicenter series of 573 surgically resected SQLC patients and we built one of the first risk classification model for SQLC, which was afterwards validated in a larger cohort of more than 1000 patients. This model, based on a combination of simple and easily available clinicopathological parameters, was able to effectively stratify resected SQLC patients in risk classes with a good prognostic accuracy. Once identified the best and worst prognostic performers, we investigated their molecular portrait, principally by next-generation sequencing (NGS), and their expression profile to identify recurrent molecular alterations and explore their association with prognosis. Sixty and forty-seven patients were evaluated as training and validation cohort, respectively. Copy number variation (CNV) was the most frequent genomic event. Molecular alterations were distributed regardless of prognosis, except from DDR2 mutations in good prognosis group and SMAD4 loss in poor prognosis group. The potentially druggable PI3KCA/mTOR axis represented the most frequently altered pathway (42%), with PI3KCA mutations and RICTOR high gain reported only in poor prognosis group. Upon transcriptome analysis, RICTOR high gain patients presented an increased pathway activity. The final aim of the overall project was to evaluate the molecular profile of outliers resected SQLC taking the advantage to adopt modern technologies in order to identify those molecular aberrations potentially able to predict the probability of disease recurrence and the efficacy of agents selectively targeting these candidate pathways. This integrated multi-step analysis performed in almost one hundred resected SQLC patients identified altered pathways with a biological impact in SQLC oncogenesis, revealing RICTOR high gain as a candidate therapeutical target for selective inhibition in SQLC

Role of mTOR signaling in tumor microenvironment. An overview

The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy

Multidisciplinary lifestyle intervention to manage pancreatic cancer-related cachexia: a case report

Pancreatic cancer remains an aggressive disease, with a poor prognosis and a high risk of incurring into cachexia. Supportive care, such as exercise, nutritional and psychological support, may be effective in reducing functional loss, psychological distress and improving nutritional status. We report the effect of 12 weeks of multimodal lifestyle intervention in a 55-year-old female, diagnosed with unresectable body/tail pancreatic cancer and metastasis in the liver, bone, lymph node and lung, to counteract cachexia. The multimodal program resulted safe and feasible. Over 12 weeks, considerable improvements were found in body weight, health-related physical fitness, nutritional status, distress scores, anxiety and depression levels. These findings highlight the potential role of integrated supportive interventions to manage metastatic cancer and cancer-induced cachexia

Adherence to dietary guidelines (DG) and body weight change (BWC) in early-stage breast cancer (EBC): A prospective trial in patients submitted to nutrition evidence-based educational intervention

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Factors influencing physical activity in cancer patients during oncological treatments: a qualitative study

Introduction: Although the literature supports the importance of physical activity in the oncological context, in Italy a large number of patients are not sufficiently active. Methods: The present study aimed to explore factors influencing an active lifestyle in cancer patients during oncological treatments. Semi-structured focus groups, including 18 patients with different cancer types, were conducted at the Oncology Unit in the University Hospital Trust of Verona (Italy). The interviews were audio-recorded, transcribed verbatim, and analyzed with content analysis. Results: According to the Health Belief Model, transcripts were categorized into the following themes: benefits, barriers, and cues to action. Patients reported a series of physical, physiological, and psychological benefits deriving from an active lifestyle. The main barriers hampering the physical activity participation were represented by treatment-related side effects, advanced disease, and some medical procedures, for example, ileostomy. Several strategies that can trigger patients to exercise were identified. Medical advice, social support from family and friends, features such as enjoyment, setting goals, and owning an animal can motivate patients to perform physical activity. At the same time, an individualized program based on patients' characteristics, an available physical activity specialist to consult, more detailed information regarding physical activity in the oncological setting, and having accessible structures were found important facilitators to implementing active behavior. Conclusions: Overall, patients have a positive view regarding physical activity, and a variety of obstacles and cues to action were recognized. Considering this information may help to improve adherence to a physical activity program over time, consequently increasing the expected benefits

Exploring the feasibility of a combined exercise program for patients with advanced lung or pancreatic cancer

Objective: This study aims to assess the safety, feasibility, and potential benefits of a combined aerobic and resistance exercise intervention for patients diagnosed with advanced pancreatic or lung cancer. Methods: A prospective, single-arm study was conducted, enrolling patients with advanced lung or pancreatic cancer. Participants engaged in a 12-week exercise intervention comprising personalized bi-weekly aerobic and resistance training tailored to individual baseline conditions. The primary study outcomes focused on safety (absence of serious adverse events) and feasibility. Secondary outcomes included assessments of functional capacity using the "Six minutes walking test", strength measured through handgrip and leg press tests, anthropometric measures including body mass index and waist-hip ratio, quality of life (QoL), and changes in blood parameters. Results: The study involved twelve patients (mean age 57.66 ​± ​7.40 years), with seven having pancreatic cancer and five having lung cancer. The recruitment rate was 50%, and assessment adherence was 100%, with an 84% adherence to the exercise program and no dropouts. No exercise-related adverse events were recorded, while three non-severe, non-exercise-related adverse events were observed: treatment-related dermatitis (Grade 2), axillary lymphadenopathy (Grade 2), and migraine (Grade 1). Significant enhancements in functional capacity, emotional well-being, and social functioning within the QoL domains were observed. Anthropometric measures, specifically waist-hip ratio and body mass index, remained stable. Conclusions: The findings suggest that a tailored 12-week exercise intervention is both feasible and safe for patients with advanced lung or pancreatic cancer. This intervention appears to enhance functional capacity, specific aspects of QoL, and contribute to maintaining body weight

Exercise levels and preferences in cancer patients: a cross-sectional study

Background: Despite the benefits related to physical exercise, large numbers of cancer patients are not sufficiently active. Methods: To investigate exercise levels and preferences in cancer patients, a cross-sectional study was conducted on a random sample of 392 cancer outpatients who anonymously completed a questionnaire investigating general and medical characteristics, and expressed willingness to participate in exercise programs. Current exercise levels were estimated with the Leisure Score Index (LSI). Results: Most patients (93%) were insufficiently active but 80% declared an interest in exercise programs. Patients preferred oncologist-instructed programs and specified particular exercise needs. Multivariate logistic regression showed that willingness to exercise was associated with education (OR: 1.87; 95% CI: 1.15-3.04 beyond age 14 years vs. up to 14 years) and current physical activity (OR: 1.92; 95% CI: 1.92-3.63 for sweat-inducing activity >2 times/week vs. <1 time/week). Patients given chemotherapy were less inclined to exercise (OR: 0.45; 95% CI: 0.23-0.86) than those who did not. LSI was lower if cancer stage was advanced (β: -0.36; 95% CI: -0.75 to -0.02) than if it was in remission. High LSI was also associated with longer education, lower BMI, and longer time after diagnosis. Conclusion: Cancer patients are insufficiently active but are willing to participate in personalized exercise programs. Information from this survey may help in designing personalized interventions so these patients will achieve sufficient exercise

Biofilm formation by Salmonella enteritidis at different incubation temperatures

Background: The genus Salmonella, associated with poultry products, is considered the leading cause of foodborne outbreaks in humans in many countries. In Brazil, Salmonella Enteritidis (SE) is the serovar remains as one most frequently isolated from humans, and it is also a major serovar found in animals, food, animal feed, and environmental samples, despite all the efforts to control this pathogen. Also, the bacterium is able to form biofilms on different surfaces, protecting cells from both cleaning and sanitizing procedures in the food industries. This study aimed to verify the ability of Salmonella Enteritidis isolates to form biofilm on polystyrene at different incubation temperatures. Materials, Methods & Results: A total of 171 SE samples were isolated from foodborne outbreaks (foods and stool cultures) and poultry products between 2003 and 2010. The biofilm-forming ability of samples was measured at four different temperatures (3°C, 9ºC, 25ºC, and 36ºC), for 24 h, simulating temperatures usually found in poultry slaughterhouses. Later, 200 μL of each bacterial suspension was inoculated, in triplicate, onto 96-well, flat-bottomed sterile polystyrene microtiter plates, washed, after that, the biofilm was fixed with methanol. The plates were dried at ambient temperature, stained with 2% Hucker’s crystal violet. Afterwards, absorbance was read using an ELISA plate reader and the optical density (OD) of each isolate was obtained by the arithmetic mean of the absorbance of three wells and this value was compared with the mean absorbance of negative controls (ODnc). The following classification was used for the determination of biofilm formation: no biofilm production, weak biofilm production, moderate biofilm production and strong biofilm production. Results demonstrated all isolates from stool cultures and foods involved in foodborne outbreaks, at least one of the four temperatures tested, were able to form biofilm, even at 3°C, undescribed as possible for the growth of SE. SE strains from poultry products also formed biofilm at least at one of the temperatures. Discussion: The prevention of biofilms formation is very important, once they can be difficult to remove from utensils and food equipment surfaces, becoming a chronic source of microbial contamination of foods, possible dissemination of diseases, and increase of resistance to cleaning and sanitization procedures. A high ability for biofilm formation on plastic surfaces was observed. We may consider that Salmonella has the capacity to bind to surfaces, with relevant impacts on public health. Although biofilm formation could be affected by temperature, most of the SE isolates analyzed in our study were strong biofilm producers at all temperatures, including at 3°C, a temperature used for food preservation and until then not acknowledged as worrisome regarding the development of Salmonella spp. There is a common sense that maintenance of food at low temperatures, particularly below 5°C, is safer to consumers as low temperatures reduce microbial multiplication. However, our results show that the growth of SE in its sessile form is possible under refrigeration. These findings lead to the assumption that the ability of SE to form biofilms, especially at low temperatures, is related to its endurance in inhospitable environments, eventually infecting humans, and that may be one of the factors associated with the high prevalence of this serovar in outbreaks of foodborne diseases. To our knowledge, this is the first publication about biofilm formation by Salmonella Enteritidis at 3ºC