Evaluating the consequences of critically ill patients with pediatric cancer at Aliasghar Children's Hospital.

Background: Despite significant progress in supportive care and advancements in chemotherapy treatments, cancer remains a leading cause of mortality in children. The objective of this study was to assess the potential correlation between various risk factors and the consequences of patients with pediatric cancer who were admitted to the pediatric intensive care unit (PICU). Methods: The present investigation is a retrospective cohort study that examined children with cancer who were between the ages of 1 month and 17 years and had been admitted to the PICU. Demographic and clinical information of all patients, including such as the age, type of cancer, sex, BMI, history of specific disease, PICU admission time, disease condition on PICU admission, patient's status at PICU admission, and number of organ failures, were extracted from each patient file. Results: The number of pediatric oncology patients admitted to the PICU was 127. The highest mortality rate was observed among children with heart problems (75%), followed by CNS involvement (54.2%) and sepsis (42.9%). The study found that various factors had a significant effect on the outcomes of patients who were admitted to the PICU, including but not limited to the primary type of malignancy, disease status, indications for hospital admission, patient's condition, inpatients' length of stay (LOS), tumor type, and the extent of organ failure at the time of admission to the PICU. Conclusion: Despite recent advancements in healthcare, the prognosis of patients admitted to the PICU in underdeveloped areas remains suboptimal in comparison to those in developed regions. Poor outcomes were found to be significantly associated with various factors, including the primary type of malignancy, disease status, the reason for admission to the PICU, patient's condition, LOS, tumor type, and the extent of organ failure, especially in cases involving hematological malignancies.

Omission of 5-Fluorouracil Bolus From Multidrug Regimens for Advanced Gastrointestinal Cancers: A Multicenter Cohort Study.

BACKGROUND: 5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus. The purpose of this study was to determine whether omission of the 5-FU bolus was associated with a difference in survival and toxicity. METHODS: A real-world database from Flatiron Health was queried for patients with advanced colorectal, gastroesophageal, and pancreatic cancers who received first-line FOLFOX, FOLFIRI, and FOLFIRINOX regimens. Cox proportional hazards and Kaplan-Meier analyses were performed to compare survival outcomes between patients who received the 5-FU bolus and those who did not. Inverse probability of treatment weighted (IPTW) analysis was performed to adjust for treatment selection bias. RESULTS: This study included 11,765 patients with advanced colorectal (n=8,670), gastroesophageal (n=1,481), and pancreatic (n=1,614) cancers. Among all first-line 5-FU multidrug regimens, 10,148 (86.3%) patients received a 5-FU bolus and 1,617 (13.7%) did not. After IPTW analysis, we found that omitting the bolus was not associated with a decrease in overall survival (hazard ratio, 0.99; 95% CI, 0.91-1.07; P=.74). However, omitting the bolus was associated with reductions in neutropenia (10.7% vs 22.7%; P<.01), thrombocytopenia (11.2% vs 16.1%; P<.01), and use of granulocyte colony-stimulating factors after treatment (19.6% vs 29.1%; P<.01). CONCLUSIONS: After adjusting for baseline clinical factors, we found that omission of the 5-FU bolus from FOLFOX, FOLFIRI, and FOLFIRINOX regimens was not associated with decreased survival, but resulted in decreased toxicity and possible health care savings.

Targeted Therapy with Polymeric Nanoparticles in PBRM1-Mutant Biliary Tract Cancers: Harnessing DNA Damage Repair Mechanisms.

Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10% of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

Gynecological brachytherapy hybrid training: The Tata Memorial Centre and BrachyAcademy experience.

PURPOSE: The lack of training is a significant barrier to practicing brachytherapy (BT). Tata Memorial Centre, alongside international BT experts and BrachyAcademy, developed a hybrid gynecological BT training module. This study outlines the preparation, organization, and execution of the 2022-2023 Mumbai training, evaluates its effectiveness, and highlights areas for improvement. MATERIALS AND METHODS: Participants were radiation oncologists (RO) and medical physicists (MP) with experience in gynecological BT aiming to transition to image-guided brachytherapy (IGBT). The training covered cervical, endometrial, vaginal, vulvar, periurethral cancers, and pelvic reirradiation. The hybrid course included online pre and postcourse homework assignments, a live workshop with hands-on training, a 6-month online follow-up, and a 12-month opportunity to share the transition experience. RESULTS: The December 2022 Mumbai live workshop spanned 2.5 days, attracting 39 participants from 8 countries (Asia, Africa, Australia/Oceania). Feedback rated the course 9/10, with 78% fully meeting expectations. Forty-four percent suggested extending hands-on training. At the 6-month follow-up, response rates were low (33% RO, 11% MP). Among responding RO, 70% reported practice changes after attending the course, 40% implemented IGBT concepts in clinical practice, and 50% increased confidence in image-guided procedures. Overall, 45% of respondent sites could strengthen their intracavitary/interstitial program, while others faced limitations due to lack of access to advanced BT applicators. CONCLUSION: The hybrid gynecological BT training concept was successfully executed. Areas for improvement include extending hands-on training and enhancing participant engagement postcourse. Structured steps beyond training may be needed to improve the utilization of advanced brachytherapy for gynecological cancers.

Reasons for Surgical Attrition Among Nonmetastatic Upper Gastrointestinal Cancer Patients: A Single Institutional Experience.

INTRODUCTION: Upper gastrointestinal (UGI) cancers require multidisciplinary treatment, but surgery provides the only potentially curative option. We sought to understand reasons for attrition before surgery within our regional hospital network. METHODS: We performed chart reviews of patients (age 18-80) with stage I-III UGI cancers (gastroesophageal junction, gastric, and hepatopancreatobiliary adenocarcinomas) in our multihospital cancer registry from 2015 to 2021. Our primary outcome was reasons for surgical attrition. Univariable analysis identified factors related to surgical attrition and the Kaplan-Meier method estimated overall survival based on surgery receipt. RESULTS: Seven hundred and ninety-two patients were included in our analysis, of whom 107 (13.5%) did not undergo curative surgery. Reasons for not undergoing surgery included medical comorbidities (30.8%), patient preference/nonmedical barriers (24.3%, which included: not interested without further explanation, worried about complications, nonadherence to appointments, insurance issues, did not wish for blood transfusion, lack of social support, preferring home care, and worried about recurrence), psychosocial (5.6%), progression while on neoadjuvant therapy or waiting for transplant (15.0% and 7.5%), poor performance status (3.7%), side effects of neoadjuvant therapy (3.7%), and death unrelated to treatment or unknown cause (9.4%). Nonsurgical management was not associated with race, socioeconomic status, or distance traveled for care. Survival was greatly improved for patients who underwent surgery (158 vs. 63 weeks, p < 0.05). CONCLUSION: Nearly one in seven patients (18-80 years old) with UGI cancers evaluated at our academic cancer center did not undergo surgical resection. Reasons for surgical attrition included potentially modifiable issues, and addressing these barriers could help overcome inequities in cancer treatment and survival.

Circular RNAs in human diseases.

Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back-splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs' functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in-depth examination of circRNAs, focusing first on their involvement in non-neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs' roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.

The relationship between the tertiary lymphoid structure and immune-infiltrating cells in gastrointestinal cancers: A systematic review and meta-analysis.

OBJECTIVES: This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers. METHODS: We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis. FINDINGS: We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T-cell related markers, including CD3, CD4, CD8, CD45RO; B-cell related markers, such as CD11c and CD20; and dendritic cell-related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor-infiltrating lymphocytes. CONCLUSION: The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high-quality and multicenter clinical studies need to be conducted.

Comparative Assessment of Lipid Peroxidase in Oral Cancer and Oral Potentially Malignant Disorders.

Introduction Oral potentially malignant disorders (OPMD) are abnormally altered tissues that could potentially develop into oral cancer. From the literature, it is understandable that not all OPMDs develop into oral cancer. Hence, it is essential to identify the high-risk lesions that are more likely to develop into oral cancer. Lipid peroxidase (LPO) is a byproduct of phospholipid metabolism, and its levels are an oxidative stress marker that can probably help us predict the onset of cancer in OPMDS. This study aimed to assess the levels of LPO in OPMD, oral cancer, and normal patients. Materials and methods The sample size estimated was 15 per group. There were four groups in total. The estimation was done with the Abbkine LPO enzyme-linked immunosorption assay (ELISA) kit (Atlanta, Georgia, USA). An enzyme-substrate reaction was carried out, and the degree of the color change was measured using a microplate reader. The values were tabulated, and statistics were carried out using Statistical Package for Social Sciences (SPSS) version 26.0 (IBM Corp., Armonk, NY, USA). Both descriptive and inferential statistics were carried out. Results LPO levels (nmol/L) in each of the four groups were as follows: Group 1 (oral cancer): 171.86±78.86, Group 2 (controls): 71.66±28.36, Group 3: (oral leukoplakia): 127.50±103.53, and Group 4 (oral submucous fibrosis and oral lichen planus): 100.39±41.06. The results, when compared, were statistically significant (P< 0.05). Discussion From the above results, it is understandable that oral cancer patients experience increased oxidative stress compared to the OPMD group. The current study concluded that the obtained results showed differences in LPO levels, suggesting LPO could be used as a marker and screening tool to assess the rate and severity of cellular damage in patients with oral potentially malignant disorders.

Immunotherapeutic Innovations in Clear Cell Renal Cell Carcinoma: Current Strategies and Future Directions.

Approximatively 80% of kidney cancers globally are clear cell kidney cancers (ccRCCs), with 80% of these malignancies featuring an inactivating mutation of the Von Hippel-Lindau gene. This genetic alteration leads to the stabilization of hypoxia inducible factors 1 and 2 alpha (HIF 1 and 2α), resulting in the over-expression of target genes such as vascular endothelial growth factor (VEGF), which is crucial for angiogenesis. As a result, ccRCCs are highly vascularized and serve as models for anti-angiogenic treatments (AAT). Current AAT therapies comprise antibodies targeting VEGFs, tyrosine kinase inhibitors (TKi) (Sunitinib) that target neo-angiogenesis receptors, and competitive inhibitor receptors (Aflibercept) that trap VEGFA and PlGF. The over-expression of VEGF and related members such as VEGFC significantly influences angiogenesis, lymph-angiogenesis, and immune tolerance. This has resulted in the approval of various immune checkpoint inhibitors (known as anti-PD-1, anti-PD-L1, and anti-CTLA-4) as viable treatment options for kidney cancer. Despite these advances, ccRCC remains challenging to treat adequately. Thus, future research is imperative to better understand the biology and pathophysiology of RCC, the tumor microenvironment, and mechanisms of resistance, with the aim of developing new therapies.

Navigating the landscape of HPV-associated cancers: From epidemiology to prevention.

Human Papillomavirus (HPV) is a widespread infection associated with various cancers, including cervical, oropharyngeal, anal, and genital cancers. This infection contributes to 5 % of global cancer cases annually, affecting approximately 625,600 women and 69,400 men. Cervical cancer remains the most prevalent HPV-linked cancer among females, with the highest incidence seen in low and middle-income countries (LMICs). While most HPV infections are transient, factors such as HPV variants, age, gender, and socioeconomic status influence transmission risks. HPV is categorized into high-risk (HR-HPV) and low-risk types, with strains like HPV 16 and 18 displaying distinct demographic patterns. The intricate pathogenesis of HPV involves genetic and epigenetic interactions, with HPV oncogenes (E6 and E7) and integration into host DNA playing a pivotal role in driving malignancies. Early diagnostics, utilizing HPV DNA testing with surrogate markers such as p16, and advanced molecular techniques like PCR, liquid biopsy, and NGS, significantly impact the management of HPV-induced cancers. Effectively managing HPV-related cancers demands a multidisciplinary approach, including immunotherapy, integrating current therapies, ongoing trials, and evolving treatments. Prevention via HPV vaccination and the inclusion of cervical cancer screening in national immunization programs by conventional Pap smear examination and HPV DNA testing remains fundamental.Despite the preventability of HPV-related cancers, uncertainties persist in testing, vaccination, and treatment. This review article covers epidemiology, pathogenesis, diagnostics, management, prevention strategies, challenges, and future directions. Addressing issues like vaccine hesitancy, healthcare disparities, and advancing therapies requires collaboration among researchers, healthcare providers, policymakers, and the public. Advancements in understanding the disease's molecular basis and clinical progression are crucial for early detection, proper management, and improved outcomes.

Chimeric antigen receptor (CAR) T-cell therapy: an overview for nurses.

Chimeric antigen receptor (CAR) T-cell therapy is a relatively new and innovative immunotherapy for haemato-oncological diseases. In the UK, CAR T-cell therapy can be used to treat some patients with relapsed or refractory acute lymphoblastic leukaemia or diffuse large B-cell lymphoma. However, CAR T-cell therapy can have side effects that have implications for patients' physical and psychosocial well-being and may induce adverse reactions that can cause life-threatening acute toxicities. Nurses may have a significant role throughout the CAR T-cell therapy process, including in supporting patient decision-making, administering infusions, monitoring patients, identifying and managing adverse reactions, and providing follow-up care. This article provides an overview of CAR T-cell therapy and describes some of its potential side effects and adverse reactions. The authors also consider the role of the nurse and the implications for the nursing workforce in terms of meeting the needs of the increasing numbers of patients who may become eligible for this treatment as it is extended to other cancer types.

Dosimetric benefits of customised mouth-bite for head neck cancer patients undergoing modern proton therapy - An audit.

Background and aims: Proton therapy (PRT) for Head Neck Cancer (HNC), in view of the Bragg peak, spares critical structures like oral mucosa better than IMRT. In PRT, mouth-bites, besides immobilising and separating mucosal surfaces, may also negate the end-of-range effect. We retrospectively analysed the details and dosimetric impact of mouth-bites in PRT for HNC. Materials and methods: The data of consecutive HNC patients treated with IMPT from May 2020 to August 2022 were studied retrospectively. Details of the mouth-bite used, compliance and resultant mucosal separation were noted. Further analysis, restricted to previously unirradiated patients, comprised volumetric dosimetric data pertaining to the mouth-bite and distal mucosal surfaces. High LET zones, corresponding to 6-12 keV/micron, for mouth-bite doses above 30 Gy, were recalculated from existing plans. Results: A mouth-bite was used in 69 of 80 consecutively treated patients, ranging from 8 to 42 mm in thickness, and 12 to 52 mm in the resultant mucosal sparing. In 42 patients in whom the mouth-bite V 32 Gy was > 0, median Dmean, absolute V32, V39, V50 and V60 GyE (Gray Equivalent) of the mouth bite was 35.65 GyE (Range: 2.65 - 60 GyE), 10 cc (Range: 0.1 - 32 cc), 7.6 cc (Range: 0.1 - 30.8 cc), 5.7 cc (Range: 0.2 - 29.2 cc) and 1.45 cc (Range: 0.2 - 18.1 cc) respectively, all significantly more than the spared adjacent mucosal surface. In absence of a mouth-bite, the spared mucosa would have at least partially received the high dose received by the mouth-bite. High LET zones were noted in 12 of 48 mouth-bites. Conclusion: In PRT for HNC, mouth-bites play a vital role in improving the sparing of mucosa outside the target.

Dietary patterns and risk of oral and oropharyngeal cancers: A systematic review and meta-analysis.

Systematic evaluation of evidence assessing the role of dietary patterns on oral and oropharyngeal (OOP) cancer risk can provide a better understanding of their relationship. This systematic review of observational studies aimed to integrate the most recent evidence on the relationship between posteriori and priori dietary patterns and risk of development of OOP cancers. Studies were retrieved from Embase, PubMed, and Web of Science, and a total of 22 publications were included in the systematic review, of which 17 were included in the meta-analysis. Summary risk was estimated for highest versus lowest intakes of most common identified food groups and risk of OOP cancers using the random effect, generic inverse variance method. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) for Case-Control and Cohort studies. As per pooled analysis, consumption of healthy patterns may decrease the risk of OOP cancers by 43 %, and that of western patterns may increase this risk by 62 %. The pooling of data from ten studies analysing priori patterns and OOP cancers shows that the Mediterranean diet and diverse diet reduce the risk of such cancers, and a pro-inflammatory diet escalates the risk. On NOS, 11 studies were good in quality and 11 were moderate. Adopting a diet rich in fruits and vegetables and low intake of snacks and animal fats can potentially reduce the likelihood of developing OOP cancers. Encouraging Mediterranean diet, diverse diet and anti-inflammatory food components would be beneficial in the prevention and control of OOP cancers.

The Magnitude of Care Burden and Associated Factors in Caregivers of Children with Cancer at the Country's Largest Tertiary Referral Hospital, Ethiopia: A Cross-Sectional Study.

Objectives. Many caregivers who care for their children with cancer are affected by the care burden due to the chronic nature of the disease. This study aimed to determine the burden of care level and its related factors in the caregivers of children with cancer. Methods. A facility-based, cross-sectional study was conducted at Tikur Anbessa Specialized Hospital. Children diagnosed with cancer and treated at the hospital between July 1 and August 1, 2023, and their caregivers were included. The data were analyzed using SPSS version 25. Descriptive analysis and inferential statistics were used to summarize the data and to determine the association with the dependent variable. Statistical significance was set at P < .05. Results. A total of 208 children with cancer and their caregivers were included in the study. Most children (81, 38.9%) were below 5 years of age, and 80.3% (n = 167) of the patients came from out of Addis Ababa. The most common type of childhood cancer was haemato-lymphoid cancer (n = 117, 56.3%). The mean duration of cancer care after diagnosis was 289.55 days. The median age of caregivers was 35 ± 8.7 years, most of the caregivers were parents of the child (n = 185, 88.9%), married (n = 186, 87%), had a primary level education (n = 66, 31.7), and 87.5% (n = 182) had insufficient income for the cancer treatment cost. The average caring time was 19 to 24 hours for 76.4% (n = 159) of caregivers, and more than one-fourth of caregivers (n = 57, 27.4%) intended to abandon treatment if they couldn't get support to continue the care. The mean care burden in caregivers was 65.76 ± 14 and about, 53.4% (n = 111) and 35.1% (n = 73) of caregivers had moderate and severe care burden. Binary logistic analysis showed the factors associated with an increased care burden were the caregiver's occupational status (P = .034, 95 % CI; AOR (0.064, 0.890)), lack of support from NGOs (P = .037, 95 % CI; AOR (1.053, 5.254), and insufficient monthly income for the treatment (P = .034; 95% CI; AOR (0.064, 0.896)). Conclusion. Most of the caregivers of children with cancer were parents and had insufficient income for the treatment. More than one-fourth had an intention to abandon the cancer treatment. Most caregivers had moderate to severe care burdens.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers.

Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1ß, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV's immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Epigenetic regulation of HERVs: Implications for cancer immunotherapy.

BACKGROUND: Human endogenous retroviruses (HERVs), integrated into the human genome during primate evolution, constitute approximately 8% of the human genome. Although most HERVs are non-protein-coding owing to mutations, insertions, deletions, and truncations, recent research has revealed their diverse roles in biological processes, including disease pathogenesis. OBJECTIVE: Although many HERVs remain inactive, they have been implicated in various diseases, particularly cancer, prompting an increased interest in harnessing HERVs for therapeutic purposes. This review explores the recent advancements in our understanding of the biological roles of HERVs, emphasizing their clinical relevance in cancer treatment. METHODS: Here, we discuss how the detection of transposable elements (TEs), including HERVs, by the immune system triggers innate immune responses in human cancers. CONCLUSION: Additionally, we outline recent progress in elucidating the implications of HERV activation in cancer and how targeting HERVs holds promise for anti-cancer treatments by modulating epigenetic plasticity and disrupting cancer initiation and progression.

Phytochemical Targeting of Nerve Growth Factor by Thymoquinone and Cuscutin: A Molecular Dynamics Simulation Study.

Background Nerve growth factor (NGF) is a novel target of pain therapeutics for oral cancer, and it plays a main role in the nociception of chronic pain. Surgery, along with chemotherapy or radiotherapy, is the gold standard for treating patients, but the side effects are significant as well. Newer effective interventions with natural phytochemicals could improve patient compliance and enhance the quality of life among patients with oral cancer. A literature search revealed a positive correlation between NGF and oral cancer pain. Nigella sativa (N. sativa) and Cuscuta reflexa (C. reflexa) have proven anticancer effects, but their activity with NGF is unexplored. Aims and objectives We aimed to identify the potential phytochemicals in N. sativa and C. reflexa. We also checked the NGF-blocking activity of the phytochemicals. Molecular docking and molecular dynamic (MD) simulations evaluated the binding energy and stability between the NGF protein and selected phytochemical ligands. Materials and methods We obtained protein NGF structure from UniProt (ID: 4EDX, P01138, Beta-nerve growth factor), ligand (thymoquinone) structure using PubChem ID: 10281, and ligand (cuscutin) structure using PubChem ID: 66065. Maestro protein (Schrödinger Inc., Mannheim, Germany) was used for molecular docking. Desmond Simulation Package (Schrödinger Inc., Mannheim, Germany) was used to model MD for 100 nanoseconds (ns). We have assessed the interaction between the protein and ligands by root mean square deviation (RMSD) values.  Results The interaction of thymoquinone and cuscutin with NGF was assessed. While interacting with thymoquinone, there was mild fluctuation from 0.6 Å to 2.5 Å up to 80 ns and ended up at 4.8 Å up to 100 ns. While interacting with cuscutin, mild fluctuation was seen from 0.8 Å to 4.8 Å till 90 ns and ended at 6.4 Å up to 100 ns. We found a stable interaction between our drug combination and the NGF receptor. Conclusion We have identified a stable interaction between thymoquinone, cuscutin, and NGF by our MD simulations. Hence, it could be used as an NGF inhibitor for pain relief and to control tumor progression. Further in vitro and in vivo evaluations of this novel drug combination with phytochemicals will help us understand their biological activities and potential clinical applications in oral cancer therapeutics.

Tobacco is a Leading Risk Factor for Liver and Extrahepatic Cancers in Patients With Liver Cirrhosis: A Prospective Cohort Study.

Background & aims: This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies. Methods: Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models. Results: A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6-16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33-7.38; former smokers: SHR 2.54, 95% CI 1.08-5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer. Conclusions: Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.

Factors influencing quality of life in early-stage upper gastrointestinal cancer patients in Nanchong city: a qualitative study.

OBJECTIVES: To identify the determinants of quality of life (QoL) among early-stage upper gastrointestinal cancer (UGIC) patients in Nanchong City to inform the development of targeted treatment plans. METHODS: In this retrospective study, 642 patients diagnosed with UGIC were included. A phenomenological approach was employed, involving in-depth face-to-face interviews to explore patients' real-life experiences with QoL, with an emphasis on spiritual and psychological aspects. Data analysis followed Colaizzi's seven-step method. Statistical analyses included one-way Analysis of Variance (ANOVA), t-tests, binary logistic regression, and Pearson correlation tests. RESULTS: QoL was significantly reduced in patients with early-stage GI cancer (P<0.001), with prevalent symptoms of anxiety and depression necessitating focused psychological interventions and enhanced medical care. Influential factors on QoL included income, health insurance coverage, illness duration, and levels of anxiety and depression (P<0.001). A strong negative correlation was observed between QoL scores and both the Hamilton Anxiety Scale (r=-0.7808, P<0.001) and the Hamilton Depression Rating Scale (r=-0.7493, P<0.001). CONCLUSION: This study underscores the substantial impact of anxiety and depression on the QoL of patients with early-stage UGIC. The findings provide a theoretical basis for implementing comprehensive long-term care strategies.

Glucagon-like peptide-1 (GLP-1) receptor agonists for weight management: A review for the gynecologic oncologist.

The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has experienced rapid growth amidst the obesity epidemic in the United States. While originally developed for glucose control in Type 2 Diabetes Mellitus, the scope of these agents now extends to encompass weight loss and cardiovascular risk reduction. GLP-1RAs have the potential to induce significant weight loss, in combination with lifestyle modifications, among adults who are overweight or obese. Furthermore, these agents demonstrate efficacy in ameliorating hyperglycemia, enhancing insulin sensitivity, regulating blood pressure, improving cardiometabolic parameters, mitigating kidney dysfunction, and potentially reducing the risk of several obesity-related cancers. Drug-related toxicity is primarily gastrointestinal and active management can prevent drug discontinuation. Obesity is associated both with an increased incidence of malignancy but also with decreased survival. More research is needed to evaluate the potential use of GLP-1RA to modify the endocrine function of adipocytes, regulate the chronic inflammatory state associated with obesity, and prospective applications in oncology. These agents can impact patients with gynecologic malignancies both through their direct mechanism of action as well as potential drug toxicity.