Exploring Mechanisms behind Beneficial Effects of HIPEC Treatment on Peritoneal Metastasis

Peritoneal metastasis (PM) arises from different gastrointestinal cancers and ovarian cancer. The most common primary tumor metastasizing to the peritoneum is colorectal cancer (CRC). The treatment of these patients suffering with PM depends on several factors including the extent of the disease in the peritoneal cavity. In case of a limited disease, cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) can be indicated. The concept of this treatment approach is to resect the visible tumor mass during CRS and eradicate remnant microscopic tumors via the HIPEC application. One of the two different drug regimens applied for CRC-PM are either the combination of Mitomycin C and Doxorubicin or Oxaliplatin alone. The median overall survival (OS) of patients treated with CRS/HIPEC is roughly 50 months with some long-term survivors, surviving up to 8 years. Why some patients respond better and show long-term survival remains unclear. Clinical studies indirectly suggest a better tumor control probably via the immune system most likely due to the induction of chemotherapeutics-mediated protective immune reactions. In this thesis, the direct and indirect impact of HIPEC treatment on the immune system to explain induction of tumor-specific immunity were explored. Using patient samples, a systemic inflammatory response after HIPEC and an impaired accuracy of commonly used inflammatory parameters in clinics to diagnose postoperative infectious complications were examined. Furthermore, with the specific analysis of paired (primary tumors and metastatic lesions) PM patient samples, a significant longer disease free survival (DFS) and overall survival (OS) was noticed in the patient group with a higher number of intraepithelial CD8+ T-cells in the PM tumor than with a low number. This was the basis to further investigate HIPEC-mediated effects on CD8+ T-cell infiltration in a murine PM model. The results of these experiments illustrated, that the efficacy of HIPEC was dependent on the function and presence of CD8+ T-cells. Using colorectal cancer cell lines and patient- derived tumor organoids, it was noted that heated chemotherapy (in-vitro HIPEC treatment) treatment induced immunogenic changes via enhanced expression of MHC-class I molecules and cancer testis antigens (CTA). Such immunogenic changes initiated the maturation of monocyte-derived dendritic cells and subsequently the production of intracellular IFN- by CD8+ T-cells. Overall, the work presented in this thesis might help patients suffering with PM by identifying post operation infections at an early stage using additional markers, overall reducing disease and surgery related complications. The work performed using experimental models show that HIPEC treatment seems to enhance immunogenicity of cancer cells making that can activate CD8+ T-cells. This mechanistic finding suggests that in the future patients with PM might survive better if treated with immunotherapies after HIPEC treatment as immunotherapies are known to provide sustained T-cells activity

Nutrition and Stress: Finding a Link Between Eating Habits and General Stress & Anxiety

Mental and physical health are closely connected; diet and exercise regimens can affect mental health and stress levels. Research has found links between inflammation—caused by processed foods—causing increased rates of depression. Diets high in fruits and vegetables, on the other hand, can reduce rates of depression by supporting the gut microbiome and by providing essential micronutrients and antioxidants. For our research, the investigation showed links between dietary habits and stress. The online survey was administered through word of mouth, social media, and group chats. The survey gathered information pertaining to the demographics, diet and exercise habits, and mental wellness of 194 participants over the course of three weeks. The results were analyzed using SPSS version 25.0. The Pearson coefficient was used to examine correlations between students\u27 dietary and lifestyle choices and overall mental well-being. Our results displayed that breakfast would improve mood because skipping breakfast leads to the brain producing excess cortisol. Based on our findings, there was a strong negative correlation between eating breakfast and negative emotions such as eating breakfast and feeling nervousness ( r = -0.186) (P\u3c0.01), eating breakfast and feeling restless (r = -0.210) (P\u3c0.01), and eating breakfast and feeling depressed ( r = -0.155) (P\u3c0.01) . To conclude, eating healthy foods regularly can positively affect brain function; students with healthy eating and exercise patterns have demonstrated reduced stress and anxiety.https://orb.binghamton.edu/research_days_posters_2022/1096/thumbnail.jp

Corruption et investissement externe direct au Brésil

 O Brasil até 2010 ficou entre os 10 principais países receptores de IED, mas de 2010 a 2014, perdeu posições no ranking dos países receptores de IED. Um dos fatores econômicos que os investidores analisam na escolha do país receptor é a corrupção, que é um dos principais desafios enfrentados pelo Brasil. O presente trabalho tem como objetivo analisar a percepção de executivos de empresas multinacionais sobre o quanto a corrupção influenciou no IED do Brasil no período de 2010 a 2014. Para tanto, utilizou-se uma metodologia de pesquisa em duas partes complementares. Na primeira foram realizadas entrevistas com dois executivos de multinacionais de capital estrangeiro. Na segunda foram enviados questionários para multinacionais de capital estrangeiro atuantes no Brasil. Após a análise dos dados coletados de ambas as pesquisas percebeu-se que a corrupção é um fator condicionante para a entrada de IED no país e que o Brasil precisa combater e controlar a corrupção, pois a mesma afeta a qualidade dos serviços prestados, a infraestrutura e o investimento global no país

Altered emotion processing circuits during the anticipation of emotional stimuli in women with borderline personality disorder

Borderline personality disorder (BPD) is associated with disturbed emotion processing, typically encompassing intense and fast emotional reactions toward affective stimuli. In this study, we were interested in whether emotional dysregulation in BPD occurs not only during the perception of emotional stimuli, but also during the anticipation of upcoming emotional pictures in the absence of concrete stimuli. Eighteen female patients with a diagnosis of BPD and 18 healthy control subjects anticipated cued visual stimuli with prior known emotional valence or prior unknown emotional content during functional magnetic resonance imaging. Brain activity during the anticipation of emotional stimuli was compared between both groups. When anticipating negative pictures, BPD patients demonstrated less signal change in the left dorsal anterior cingulate cortex (dACC) and left middle cingulate cortex (MCC), and enhanced activations in the left pregenual ACC, left posterior cingulate cortex (PCC) as well as in left visual cortical areas including the lingual gyrus. During the anticipation of ambiguously announced stimuli, brain activity in BPD was also reduced in the left MCC extending into the medial and bilateral dorsolateral prefrontal cortex. Results point out that deficient recruitment of brain areas related to cognitive-emotional interaction already during the anticipation phase may add to emotional dysregulation in BPD. Stronger activation of the PCC could correspond to an increased autobiographical reference in BPD. Moreover, increased preparatory visual activity during negative anticipation may contribute to hypersensitivity toward emotional cues in this disorder

Prevalência de vírus respiratório na asma aguda na sala de emergência : estudo piloto

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