Treatment Of Cancer Research Articles

Application of machine learning in the analysis of multiparametric MRI data for the differentiation of treatment responses in breast cancer: retrospective study.

The objective of this study is to develop and validate a multiparametric MRI model employing machine learning to predict the effectiveness of treatment and the stage of breast cancer. The study encompassed 400 female patients diagnosed with breast cancer, with 200 individuals allocated to both the control and experimental groups, undergoing examinations in Shenzhen, China, during the period 2017-2023. This study pertains to retrospective research. Multiparametric MRI was employed to extract data concerning tumor size, blood flow, and metabolism. The model achieved high accuracy, predicting treatment outcomes with an accuracy of 92%, sensitivity of 88%, and specificity of 95%. The model effectively classified breast cancer stages: stage I, 38% ( P = 0.027); stage II, 72% ( P = 0.014); stage III, 50% ( P = 0.032); and stage IV, 45% ( P = 0.041). The developed model, utilizing multiparametric MRI and machine learning, exhibits high accuracy in predicting the effectiveness of treatment and breast cancer staging. These findings affirm the model's potential to enhance treatment strategies and personalize approaches for patients diagnosed with breast cancer. Our study presents an innovative approach to the diagnosis and treatment of breast cancer, integrating MRI data with machine learning algorithms. We demonstrate that the developed model exhibits high accuracy in predicting treatment efficacy and differentiating cancer stages. This underscores the importance of utilizing MRI and machine learning algorithms to enhance the diagnosis and individualization of treatment for this disease.

Functional outcomes and quality of life following open versus laparoscopic versus robot-assisted versus transanal total mesorectal excision in rectal cancer patients: a systematic review and meta-analysis.

The standard surgical treatment for rectal cancer is total mesorectal excision (TME), which may negatively affect patients' functional outcomes and quality of life (QoL). However, it is unclear how different TME techniques may impact patients' functional outcomes and QoL. This systematic review and meta-analysis evaluated functional outcomes of urinary, sexual, and fecal functioning as well as QoL after open, laparoscopic (L-TME), robot-assisted (R-TME), and transanal total mesorectal excision (TaTME). A systematic review and meta-analysis, based on the preferred reporting items for systematic reviews and meta-analysis statement, were conducted (PROSPERO: CRD42021240851). A literature review was performed (sources: PubMed, Medline, Embase, Scopus, Web of Science, and Cochrane Library databases; end-of-search date: September 1, 2023), and a quality assessment was performed using the Methodological index for non-randomized studies. A random-effects model was used to pool the data for the meta-analyses. Nineteen studies were included, reporting on 2495 patients (88 open, 1171 L-TME, 995 R-TME, and 241 TaTME). Quantitative analyses comparing L-TME vs. R-TME showed no significant differences regarding urinary and sexual functioning, except for urinary function at three months post-surgery, which favoured R-TME (SMD [CI] -0.15 [-0.24 to -0.06], p = 0.02; n = 401). Qualitative analyses identified most studies did not find significant differences in urinary, sexual, and fecal functioning and QoL between different techniques. This systematic review and meta-analysis highlight a significant gap in the literature concerning the evaluation of functional outcomes and QoL after TME for rectal cancer treatment. This study emphasizes the need for high-quality, randomized-controlled, and prospective cohort studies evaluating these outcomes. Based on the limited available evidence, this systematic review and meta-analysis suggests no significant differences in patients' urinary, sexual, and fecal functioning and their QoL across various TME techniques.

Survival outcome of esophagectomy and chemoradiotherapy for resectable esophageal squamous cell carcinoma in patients >75 years of age.

The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.

Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions.

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Emergence of Quantum Dots as Innovative Tools for Early Diagnosis and Advanced Treatment of Breast Cancer.

Quantum dots (QDs) semiconducting nanomaterials, have garnered attention due to their distinctive properties, including small size, high luminescence, and biocompatibility. In the context of triple-negative breast cancer (TNBC), notorious for its resistance to conventional treatments, QDs exhibit promising potential for enhancing diagnostic imaging and providing targeted therapies. This review underscores recent advancements in the utilization of QDs in imaging techniques, such as fluorescence tomography and magnetic resonance imaging, aiming at the early and precise detection of tumors. Emphasis is placed on the significance of QD design, synthesis and functionalization processes as well as their use in innovative strategies for targeted drug delivery, capitalizing on their ability to selectively deliver therapeutic agents to cancer cells. As the research in this field advances rapidly, this review covers a classification of QDs according to their composition, the characterization techniques than can be used to determine their properties and, subsequently, emphasizes recent findings in the field of TNBC-targeting, highlighting the imperative need to address challenges, like potential toxicity or methodologies standardization. Collectively, the findings explored thus far suggest that QDs could pave the way for early diagnosis and effective therapy of TNBC, representing a significant stride toward precise and personalized strategies in treating TNBC.

Marine algae-derived characterized bioactive compounds as therapy for cancer: A review on their classification, mechanism of action, and future perspectives.

In 2022, there were around 20 million new cases and over 9.7 million cancer-related deaths worldwide. An increasing number of metabolites with anticancer activity in algae had been isolated and identified, which were promising candidates for cancer therapy. Red algae are well-known for the production of brominated metabolites, including terpenoids and phenols, which have the capacity to induce cell toxicity. Some non-toxic biological macromolecules, including polysaccharides, are distinct secondary metabolites found in many algae, particularly green algae. They possess anticancer activities by inhibiting tumor angiogenesis, stimulating the immune response, and inducing apoptosis. However, the structure-activity relationship between these components and antitumor activity, as well as certain taxa within the algae, remains relatively unstudied. This work is based on the reports published from 2003 to 2024 in PubMed and ISI Web of Science databases. A comprehensive review of the characterized algal anticancer active compounds, together with their structure and mechanism of action was performed. Also, their structure-activity relationship was preliminarily summarized to better assess their potential properties as a natural, safe bioactive product to be used as an alternative for the treatment of cancers, leading to new opportunities for drug discovery.

Screening for Breast Cancer: A Comparative Review of Guidelines.

Breast cancer is the most common malignancy diagnosed in the female population worldwide and the leading cause of death among perimenopausal women. Screening is essential, since earlier detection in combination with improvements in breast cancer treatment can reduce the associated mortality. The aim of this study was to review and compare the recommendations from published guidelines on breast cancer screening. A total of 14 guidelines on breast cancer screening issued between 2014 and 2022 were identified. A descriptive review of relevant guidelines by the World Health Organization (WHO), the U.S. Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), the National Comprehensive Cancer Network (NCCN), the American College of Obstetricians and Gynecologists (ACOG), the American Society of Breast Surgeons (ASBrS), the American College of Radiology (ACR), the Task Force on Preventive Health Care (CTFPHC), the European Commission Initiative on Breast Cancer (ECIBC), the European Society for Medical Oncology (ESMO), the Royal Australian College of General Practitioners (RACGP) and the Japanese Journal of Clinical Oncology (JJCO) for women both at average and high-risk was carried out. There is a consensus among all the reviewed guidelines that mammography is the gold standard screening modality for average-risk women. For this risk group, most of the guidelines suggest annual or biennial mammographic screening at 40-74 years, while screening should particularly focus at 50-69 years. Most of the guidelines suggest that the age limit to stop screening should be determined based on the women's health status and life expectancy. For women at high-risk, most guidelines recommend the use of annual mammography or magnetic resonance imaging, while the starting age should be earlier than the average-risk group, depending on the risk factor. There is discrepancy among the recommendations regarding the age at onset of screening in the various high-risk categories. The development of consistent international practice protocols for the most appropriate breast cancer screening programs seems of major importance to reduce mortality rates and safely guide everyday clinical practice.

Synthesis, Characterization, and Cytotoxicity Evaluation of Novel Water-Soluble Cationic Platinum(II) Organometallic Complexes with Phenanthroline and Imidazolic Ligands.

Platinum-based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water-soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1-C2H4OEt)(phen)] (1, phen=1,10-phenanthroline) precursor, specifically [Pt(NH3)(η1-C2H4OEt)(phen)]Cl (2), [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl (3), and [Pt(1-hexyl-1H-benzo[d]imidazole)(η1-C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki-1), and normal human renal cells (HK-2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki-1) among the tested complexes, compared to healthy cells (HK-2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum-based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties.

Multistage Nanocarrier Based on an Oil Core-Graphene Oxide Shell.

Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer treatment is the ability to bring such molecules within each single cancer cell, which requires accumulation in the peritumoral region followed by homogeneous spreading within the entire tissue. In the last decades, nanotechnology has emerged as a powerful tool due to its ability to protect the drug during blood circulation and allow enhanced accumulation around the leaky regions of the tumor vasculature. However, the ideal size for accumulation of around 100 nm is too large for effective penetration into the dense collagen matrix. Therefore, we propose a multistage system based on graphene oxide nanosheet-based quantum dots (GOQDs) with dimensions that are 12 nm, functionalized with hyaluronic acid (GOQDs-HA), and deposited using the layer-by-layer technique onto an oil-in-water nanoemulsion (O/W NE) template that is around 100 nm in size, previously stabilized by a biodegradable polymer, chitosan. The choice of a biodegradable core for the nanocarrier is to degrade once inside the tumor, thus promoting the release of smaller compounds, GOQDs-HA, carrying the adsorbed anticancer compound, which in this work is represented by curcumin as a model bioactive anticancer molecule. Additionally, modification with HA aims to promote active targeting of stromal and cancer cells. Cell uptake experiments and preliminary penetration experiments in three-dimensional microtissues were performed to assess the proposed multistage nanocarrier.

MDB-48. A SINGLE INSTITUTION EXPERIENCE OF CIPN MEASURED BY THE PED-MTNS IN CHILDREN AND ADOLESCENTS WITH MEDULLOBLASTOMA TREATED ON A TRIAL USING SIMILAR DOSING OF VINCRISTINE AND CISPLATIN FOR ALL PATIENTS

Abstract BACKGROUND Standard treatment for medulloblastoma in patients >3 years of age consists of tumor resection, radiation and chemotherapy using vincristine, cisplatin, cyclophosphamide +/- CCNU. Vincristine and Cisplatin are known to cause chemotherapy induced peripheral neuropathy (CIPN). The prevalence of CIPN in children with non-CNS cancers can be measured using the pediatric-modified Total Neuropathy Score (ped-mTNS). The purpose of this observational, retrospective pilot design is twofold: to investigate the prevalence of CIPN in children with medulloblastoma receiving neurotoxic chemotherapy, and to examine the feasibility of using the ped-mTNS as a measurement tool in this population. METHODS Data was manually extracted from medical records and entered into a REDCap database for analysis. The percent of patients successfully tested and clinical inferences made from ped-mTNS testing results were used to determine feasibility and barriers to use. A total of 33 medulloblastoma patients >3 years of age were treated from 6/2013 - 6/2021 at Children’s Minnesota. Of those, 18 received testing using the ped-mTNS during chemotherapy treatment. RESULTS During cancer treatment, 54.5% of the cohort of patients received ped-mTNS testing. The average age of children tested was 10.26 (4.39) years with a majority being male (79%), and non-Hispanic white race/ethnicity (89%). Of the tested participants, 61.1% had more than one measurement. For those patients tested at multiple timepoints, 72.7% demonstrated worsening ped-mTNS scores while on chemotherapy treatment. Therapists recorded inferences relating to neuropathy in 88.1% of testing occurrences with questions of accuracy recorded in 31.3% of testing occurrences. Barriers to use of results included confounding impairments that may occur as a result of the primary tumor, post-surgical changes, and radiation. CONCLUSIONS Using the ped-mTNS is feasible in children and adolescents with medulloblastoma. The ped-mTNS scores indicated that children with medulloblastoma, treated with Vincristine and Cisplatin, experience worsening neuropathy while undergoing chemotherapy treatment.

Enhancing Therapeutic Efficacy in Cancer Treatment: Integrating Nanomedicine with Autophagy Inhibition Strategies

Enhancing Therapeutic Efficacy in Cancer Treatment: Integrating Nanomedicine with Autophagy Inhibition Strategies

QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Younger age at diagnosis and cranial radiation therapy are associated with neurocognitive late complications in survivors of pediatric brain tumors (PBT). Less is known about the association between neurocognition and epileptic seizures, with the latter affecting 27% of 5-year survivors. This study aimed to explore whether epileptic seizures exacerbate neurocognitive late complications beyond treatment and demographic factors. METHODS Fifty-nine survivors of PBT who had experienced at least one epileptic seizure, and a control group of survivors matched on sex, age at diagnosis, and cancer treatment, all diagnosed at Skåne University Hospital, were included in the study. Demographic and clinical variables, along with neurocognitive measures of verbal and non-verbal reasoning, cognitive processing speed, working memory, and cognitive flexibility were collected from medical records. Neuropsychological scores, assessed on average 3.68 years after diagnosis, were transformed into z-scores employing age-adjusted norms (m=0, sd=1). Generalized linear models, controlling for increased intracranial pressure at diagnosis and tumor localization, were used to analyze the association between epileptic seizures, cumulative use of anti-seizure medications (ASM), and neurocognition. RESULTS Experiencing any type of epileptic seizures was associated with reduced processing speed (β = -0.91z, p<0.01) and cognitive flexibility (β =-1.05z, p<0.01). Treatment with one ASM was associated with reduced cognitive processing speed (β =-0.81z, p=0.03), and treatment with two or more ASM was associated with lower scores on measures of non-verbal reasoning (β =-0.81z, p<0.01), working memory (β =-0.77z, p=0.01), processing speed (β=-1.26z, p<0.01), and flexibility (β =-1.54z, p<0.01). CONCLUSIONS Epileptic seizures and treatment with ASM were both associated with neurocognitive late complications. Optimal seizure management presents a potential modifiable factor for reducing cognitive burden in survivors of PBT.

The Evolution of Nadofaragene Firadenovec: A Review and the Path Forward

BACKGROUND: The intravesical gene therapy nadofaragene firadenovec (rAd-IFNα/Syn3) was FDA approved in 2022 for non-muscle invasive bladder cancer (NMIBC) unresponsive to frontline treatment with BCG, and the first gene therapy developed for bladder cancer. This non-replicating recombinant adenovirus vector delivers a copy of the human interferon alpha-2b gene into urothelial and tumor cells, causing them to express this pleotropic cytokine with potent antitumor effects. OBJECTIVE: To provide a historical overview describing how several decades of preclinical and clinical studies investigating the role of interferon in the treatment of bladder cancer ultimately led to the development of gene therapy with nadofaragene for NMIBC. METHODS: We conducted a review of the literature using PubMed, Google Scholar, and ClinicalTrials.gov to summarize our knowledge of the evolution of interferon-based therapy in NMIBC. RESULTS: The FDA approval of this therapy represents an important landmark in urologic oncology and several decades of research dedicated to the study of interferon’s direct and indirect antitumor properties in NMIBC. The data gathered from the phase 1, 2, and 3 clinical trials continue to provide additional insights into the precise mechanisms underlying both the efficacy of and resistance to nadofaragene. CONCLUSIONS: Nadofaragene leverages the cytotoxic, anti-angiogenic, and immune-modulatory roles of interferon to effectively treat NMIBC that is resistant to BCG. Ongoing studies of resistance mechanisms and prognostic biomarkers have been promising; these will ultimately improve patient selection and allow for the modulation of factors in the tumor or immune microenvironment to further increase therapeutic response.

Defect-Rich Metastable MoS2 Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e., molybdenum disulfide (MoS2) nanozymes) with enzyme-like activity are demonstrated in animal models for cancer immunotherapy. However, in situ engineering of TAMs polarization through sufficient accumulation of free radical reactive oxygen species for immunotherapy in clinical samples remains a significant challenge. In this study, defect-rich metastable MoS2 nanozymes, i.e., 1T2H-MoS2, are designed via reduction and phase transformation in molten sodium as a guided treatment for human breast cancer. The as-prepared 1T2H-MoS2 exhibited enhanced peroxidase-like activity (≈12-fold enhancement) than that of commercial MoS2, which is attributed to the charge redistribution and electronic state induced by the abundance of S vacancies. The 1T2H-MoS2 nanozyme can function as an extracellular hydroxyl radical generator, efficiently repolarizing TAMs into the M1-like phenotype and directly killing cancer cells. Moreover, the clinical feasibility of 1T2H-MoS2 is demonstrated via ex vivo therapeutic responses in human breast cancer samples. The apoptosis rate of cancer cells is 3.4 times greater than that of cells treated with chemotherapeutic drugs (i.e., doxorubicin).

Factors Influencing Patient Decision-Making in the Treatment of Muscle-Invasive Bladder Cancer

BACKGROUND: In 2023, an estimated 82,290 individuals were diagnosed with bladder cancer in the United States. For muscle-invasive bladder cancer (MIBC), the American Urological Association recommends offering radical cystectomy with cisplatin-based neoadjuvant chemotherapy. However, patients are increasingly requesting alternative treatments. OBJECTIVE: To describe factors influencing selection of radical cystectomy with cisplatin-based neoadjuvant chemotherapy (NAC + RC), radical cystectomy monotherapy (RC), or tri-modality therapy (TMT) among patients with MIBC. METHODS: Individual, semi-structured phone interviews were conducted with 18 adults who underwent MIBC treatment at the University of North Carolina, recruiting six patients each from three treatment groups: 1) NAC + RC, 2) RC, and 3) TMT. Interview transcriptions were qualitatively analyzed using QSR NVivo, with major themes and sub-themes extracted. Patients also completed the Shared Decision-Making Questionnaire (SDM-Q-9; range 0–100). RESULTS: Concern for survival and risks, quality of life, and varied patient preferences for involvement influenced the decision-making process. Concern surrounding sexual function, bladder preservation, and urostomy bags drove patients towards TMT. High levels of shared decision-making were observed overall, with a median SDM-Q-9 score of 95 (IQR 89–100). Patients undergoing TMT reported the highest median SDM-Q-9 score (97, IQR 94–100), while those receiving radical cystectomy alone had the lowest (66, IQR 37–96). CONCLUSIONS: Patients with MIBC described a multifaceted treatment decision-making process, highlighting key influences, concerns, and unmet needs. Understanding this process can help address misconceptions and align treatment choices with patient goals. Physicians can use these insights to engage in shared decision-making, ultimately improving patient experiences and outcomes.

Aromatase inhibitors evoke periorbital allodynia in mice via calcitonin gene-related peptide and its receptors in Schwann cells

Background: Treatment with the currently recommended aromatase inhibitors (AIs) for adjuvant endocrine treatment of estrogen receptorpositive breast cancer is associated with debilitating musculoskeletal pain symptoms (AIMS) and headache. Recent evidence suggests that the proalgesic channel transient receptor potential ankyrin 1 (TRPA1) is implicated in AIMS. Here, we investigated the cellular and molecular mechanisms, including TRPA1, implicated in periorbital mechanical allodynia (PMA), a surrogate of headache-like pain, evoked by AIs in mice. Methods: C57BL6/J mice were treated with intragastric letrozole (0.05-0.5 mg/kg), exemestane (1-5 mg/kg) or anastrozole (0.02-0.2 mg/kg) and were evaluated by applying von Frey filaments to the periorbital region over the rostral portion of the eye. Some mice were pretreated (subcutaneous in the periorbital area) with receptor, channel, or enzyme inhibitors. PMA was also investigated in mice with selective silencing of Trpa1 and receptor activity modifying protein 1 [Ramp1, the component of calcitonin gene related peptide (CGRP) receptor required for its functioning] in Schwann cells (Plp-Cre+-Trpa1fl/fl and Plp-Cre+-Ramp1fl/fl mice, respectively) or trigeminal neurons (Adv-Cre+- Trpa1fl/fl and Adv- Cre+- Ramp1fl/fl mice, respectively). Results: Letrozole dose-dependently produced PMA that was attenuated by a TRPA1 antagonist (A967079) or a CGRP receptor antagonist (olcegepant), whereas indomethacin was ineffective. Selective silencing of Trpa1 in both Schwann cells and trigeminal neurons reduced letrozole- evoked PMA. Silencing of Ramp1 in Schwann cells, but not in trigeminal neurons, attenuated PMA. Inhibition of the intracellular pathway known to promote PMA by CGRP action in Schwann cells, including adenylyl cyclase (SQ-22536), nitric oxide synthase (L-NG-Nitro arginine methyl ester), and oxidative stress (N-tert-butyl-a-phenylnitrone) inhibitors reduced letrozole-evoked PMA. PMA evoked by exemestane (1, 5, 10 mg/kg i.g.) or anastrozole (0.02, 0.1, 0.2 mg/kg i.g.) Was also markedly reduced in mice with selective silencing of TRPA1 in Schwann cells and nociceptors. Conclusions: Data indicate that letrozole, targeting TRPA1 in peptidergic nerve terminals, releases CGRP that engages its receptor in adjacent Schwann cells to trigger a complex intracellular pathway that results in TRPA1 activation and the ensuing ROS release to sustain PMA. Should these mechanisms be present in patients, their inhibition may ameliorate cephalic mechanical allodynia associated with aromatase inhibitors-induced headaches.

Influence of the COVID-19 Pandemic on Patients with Rectal Cancer.

Objectives: The COVID-19 pandemic and its associated restrictions have resulted in delayed diagnoses across various tumor entities, including rectal cancer. Our hypothesis was based on the expectation of a reduced number of primary operations due to higher tumor stages compared to the control group. Methods: In a single-center retrospective study conducted from 1 March 2018 to 1 March 2022, we analyzed 120 patients with an initial diagnosis of rectal cancer. Among them, 65 patients were part of the control group (pre-COVID-19), while 55 patients were included in the study group (during the COVID-19 pandemic). We compared tumor stages, treatment methods, and complications, presenting data as absolute numbers or mean values. Results: Fewer primary tumor resections during the COVID-19 pandemic (p = 0.010), as well as a significantly lower overall number of tumor resections (p = 0.025) were seen compared to the control group. Twenty percent of patients in the COVID-19 group received their diagnosis during lockdown periods. These patients presented significantly higher tumor stages (T4b: 27.3% vs. 6.2%, p = 0.025) compared to the control group prior to the pandemic. In addition, more patients with angiolymphatic invasion (ALI) were identified in the COVID-19 group following neoadjuvant treatment compared to the control group (p = 0.027). No differences were noted between the groups regarding complications, stoma placement, or conversion rates. Conclusions: The COVID-19 pandemic, particularly during lockdown, appears to have contributed to delayed diagnoses, resulting in higher tumor stages and a decreased number of surgeries. The quality of rectal cancer treatment can be maintained under pandemic conditions.

Genetic risk of second malignant neoplasm after childhood cancer treatment: A systematic review.

Second malignant neoplasm (SMN) is one of the most severe long-term risks for childhood cancer survivors (CCS), significantly impacting long-term patient survival. While radiotherapy and chemotherapy are known risk factors, the observed inter-individual variability suggests a genetic component contributing to the risk of SMN. This article aims to conduct a systematic review of genetic factors implicated in the SMN risk among CCS. Searches were performed in PubMed, Scopus, and Web of Sciences. Eighteen studies were included (eleven candidate gene studies, three genome-wide association studies, and four whole exome/genome sequencing studies). The included studies were based on different types of first cancers, investigated any or specific types of SMN, and focused mainly on genes involved in drug metabolism and DNA repair pathways. These differences in study design and methods used to characterize genetic variants limit the scope of the results and highlight the need for further extensive and standardized investigations. However, this review provides a valuable compilation of SMN risk-associated variants and genes, facilitating efficient replication and advancing our understanding of the genetic basis for this major risk for CCS.

EZH2-associated tumor malignancy: A prominent target for cancer treatment.

The discussion in this review centers around the significant relationships between EZH2 and the initiation, progression, metastasis, metabolism, drug resistance, and immune regulation of cancer. Polycomb group (PcG) proteins, which encompass two primary Polycomb repressor complexes (PRC1 and PRC2), have been categorized. PRC2 consists mainly of four subunits, namely EZH2, EED, SUZ12, and RbAp46/48. As the crucial catalytic component within the PRC2 complex, EZH2 plays a pivotal role in controlling a wide range of biological processes. Overexpression/mutations of EZH2 have been detected in a wide variety of tumors. Several mechanisms of EZH regulation have been identified, including regulation EZH2 mRNA by miRNAs, LncRNAs, accessibility to DNA via DNA-binding proteins, post-translational modifications, and transcriptional regulation. EZH2 signaling triggers cancer progression and may intervene with anti-tumor immunity; therefore it has charmed attention as an effective therapeutic target in cancer therapy. Numerouss nucleic acid-based therapies have been used in the modification of EZH2. In addition to gene therapy approaches, pharmaceutical compounds can be used to target the EZH2 signaling pathway in the treatment of cancer. EZH2-associated tumor cells and immune cells enhance the effects of the immune response in a variety of human malignancies. The combination of epigenetic modifying agents, such as anti-EZH2 compounds with immunotherapy, could potentially be efficacious even in the context of immunosuppressive tumors. Summary, understanding the mechanisms underlying resistance to EZH2 inhibitors may facilitate the development of novel drugs to prevent or treat relapse in treated patients.

Ω-Shaped fiber optic LSPR coated with hybridized nanolayers for tumor cell sensing and photothermal treatment

Circulating tumor cell (CTC) in the blood is the main cause of cancer metastasis for death in cancer patients. It is extremely important for cancer diagnosis at an early stage and treatment to simultaneously detect and kill the CTCs. In this work, a new hybridized nanolayer, namely gold nanoparticle/gold nanorods@ Polydopamine (AuNPs/AuNRs@PDA), was coated on the Ω-shaped fiber optics (Ω-FO) for localized surface plasmonic resonance (LSPR) to perform tumor cell sensing and photothermal treatment (PTT). The PDA nanolayer was formed on a bare fiber optic through the self-polymerization of dopamine under mild conditions. The AuNRs and AuNPs were absorbed on the surface of the PDA nanolayer to form a hybridized nanolayer. The hybridized nanolayer-modified Ω-FO LSPR exhibited a high refractive index sensitivity (RIS) of 37.59 (a.u/RIU) and photothermal conversion efficiency. After being modified with the recognition element of aptamer, the Ω-FO LSPR was used to develop a sensitive and specifical tumor cell sensing. Under the irradiation of near-infrared light (NIR) laser, the Ω-FO LSPR can kill the captured tumor cells with the apoptotic/necrotic rate of 62.6 % and low side-effect for the nontarget cells. The FO LSPR sensor realized the dual functions of CTC sensing and PTT, which provided a new idea for the early diagnosis and treatment of cancer.