Family adjustment and resilience after a parental cancer diagnosis.

PURPOSE: To explore the resources, parents with cancer and their partners draw upon to sustain their family resilience through the cancer experience. METHODS: Fifteen participants who were parents of children aged 8 to 25 years completed phone, audio-recorded, and semi-structured interviews. Of these participants, 11 were parents diagnosed with cancer, and four were partners of a parent diagnosed with cancer. Interview questions aimed to increase understanding about how families communicate, connect, and face challenges from the cancer experience. Interview data was analysed using inductive thematic analysis to provide scope to generate themes from parent's experiences rather than to test pre-existing frameworks. RESULTS: The thematic analysis of interview transcripts generated three key themes related to family resilience: (1) adaptability to changes in roles and routines, (2) open communication within the family, and (3) accepting support from others. CONCLUSION: This study found that parents' ability to use personal resources when faced with significant challenges helped to improve the resilience of parents' family system. Further research is needed to understand the factors that influence family resilience when a parent is diagnosed with cancer. Implications for the development of targeted interventions that provide support to not only the patient, but their whole family system will be discussed.

Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.

INTRODUCTION: Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists. METHODS: Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable. CONCLUSIONS: This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.

PPIH acts as a potential predictive biomarker for patients with common solid tumors.

BACKGROUND: Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. METHODS: We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. RESULTS: Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. CONCLUSION: Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.

The relationship between fear of cancer recurrence and death anxiety among Chinese cancer patients: the serial mediation model.

AIMS: This study aims to investigate the association between fear of cancer recurrence (FCR) and death anxiety (DA) among Chinese cancer patients, while considering the mediating effects of experiential avoidance (EA) and meaning in life (MIL). METHODS: From February to June 2023, convenience sampling was used to select newly diagnosed cancer patients in a tertiary Cancer Hospital in Chinese Hunan Province as the survey objects. A total of 436 cancer patients completed the Fear of Cancer Recurrence Inventory, the Meaning in Life Questionnaire, the Acceptance and Action Questionnaire-II, and the Templer's death anxiety scale. Descriptive analysis and Pearson correlation analysis were conducted using SPSS 28.0 software. Serial mediation analysis was performed by Hayes' PROCESS macro. RESULTS: Gender, age, educational level, marital status, residence, occupation, per capita monthly household income, tumor type, and cancer stage were controlled in the model. The results revealed that fear of cancer recurrence had a significant direct effect on death anxiety (Effect = 0.075, 95% CI: 0.064 to 0.087). Additionally, three indirect pathways were identified: (1) through experiential avoidance (Effect = 0.037, 95% CI: 0.026 to 0.049), (2) through meaning in life (Effect = 0.022, 95% CI: 0.014 to 0.031), and (3) through the serial mediators involving meaning in life and experiential avoidance (Effect = 0.016, 95% CI: 0.010 to 0.023). The total indirect effect of the three mediation paths was 63.56%. CONCLUSION: Fear of cancer recurrence is a significant psychological distress experienced by cancer patients, which not only directly contributes to death anxiety but also may triggers changes, such as experiential avoidance and meaning in life. Ultimately, this comprehensive psychological distress leads to death anxiety.

Primary hepatic pleomorphic liposarcoma: Case report and literature review / Liposarcoma pleomorfo hepático primario: presentación de un caso y revisión bibliográfica

Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification. (AU)

El liposarcoma hepático primario es un tumor maligno extremadamente raro, derivado de adipocitos, y forma parte del grupo de tumores mesenquimales. Presentamos el caso de un paciente masculino de 43 años con diagnóstico de liposarcoma hepático pleomorfo con ausencia de amplificación del gen MDM2. Dos años y 6 meses después de la cirugía el paciente se encuentra asintomático. El presente caso es el primer informe de esta entidad con estudio inmunohistoquímico positivo para p16, p53, S100, vimentina y ausencia de amplificación del gen MDM2. (AU)

Tumor fibroso calcificante intestinal: reporte de caso / Intestinal calcifying fibrous tumor: case report

El tumor fibroso calcificante (TFC) es una inusual lesión benigna de origen mesenquimal que puede presentar características similares a otros tumores más comunes. El caso involucra a una mujer de 36 años con un tumor en el yeyuno proximal, inicialmente sospechoso de ser un tumor del estroma gastrointestinal (GIST). Se realiza una resección quirúrgica, revelando un nódulo bien delimitado en el borde antimesentérico con características microscópicas típicas de TFC. Las células tumorales presentaban positividad para CD34 y negatividad para demás marcadores, diferenciándolo de otras neoplasias. El TFC puede confundirse con tumores más comunes debido a su apariencia, pero un diagnóstico preciso respaldado por inmunohistoquímica es esencial. La extirpación quirúrgica completa suele ser curativa. (AU)

Calcifying fibrous tumor (CFT) is a rare benign lesion of mesenchymal origin that may present similar characteristics to other more common tumors. We present the case of a 36-year-old woman with a tumor in the proximal jejunum, initially suspected to be a gastrointestinal stromal tumor (GIST). Surgical resection was performed, revealing a well-demarcated nodule at the anti-mesenteric border with microscopic features typical of a calcifying fibrous tumor. The tumor cells were positive for CD34 and negative for other markers, differentiating it from other neoplasms. Calcifying fibrous tumors can be confused with more common tumors because of its appearance, but an accurate diagnosis supported by immunohistochemistry is essential. Complete surgical excision is usually curative. (AU)

Prospective of Mitochondrial DNA Variations in Cancer on Genomic Medicine.

Mitochondrial DNA (mtDNA) has emerged as a pivotal component in understanding the etiology and susceptibility of cancer. A recent study by Chen and colleagues delineated the germline genetic effect of mtDNA single-nucleotide polymorphisms (SNP) and haplogroups across pan-cancer risk. They identified a subset of mtSNPs and the corresponding risk score, as well as haplogroups A and M7 alongside their genetic interactions, conferring a protective effect against various cancers. These findings underscored the value of mtDNA variations as biomarkers for cancer etiology and as tools for cancer risk stratification. Future investigations are encouraged to integrate comprehensive omics data of genomics, transcriptomics, proteomics, and metabolomics, etc., from nuclear DNA with mtDNA variations, alongside single-cell and spatial technologies, to unravel the tumor mechanism and identify the drug targets. Moreover, the incorporation of polygenic risk score, that included mtDNA variations with both rare and common frequencies, and liquid biopsy-based biomarkers would enhance the predictive performance of cancer risk assessment and refine the risk stratification of population-based cancer screening. This commentary advocates for the validation across diverse populations to harness the full potential of mitochondrial genomics, and ultimately paves the prospective way for advancements in personalized cancer therapeutics and prevention strategies. See related article by Chen and colleagues, Cancer Epidemiol Biomarkers Prev 2024;33:381-8.

Unlocking the Next Frontier in Precision Oncology: Addressing Drug-Tolerant Residual Disease.

SUMMARY: Drug-tolerant residual disease (DTRD) after the initial maximal response to a systemic therapy can serve as a tumor reservoir for the development of acquired drug resistance and represents a major clinical challenge across various cancers and types of therapies. To unlock the next frontier in precision oncology, we propose a fundamental paradigm shift in the treatment of metastatic cancers with a sharpened focus towards defining, monitoring, and therapeutically targeting the DTRD state.

A Deep Learning Model for Cancer Type Prediction Sets a New Standard.

SUMMARY: Classifying tumor types using machine learning approaches is not always trivial, particularly for challenging cases such as cancers of unknown primary. In this issue of Cancer Discovery, Darmofal and colleagues describe a new tool that uses information from a clinical sequencing panel to diagnose tumor type, and show that the model is particularly robust. See related article by Darmofal et al., p. 1064 (1).

When Lightning Strikes Twice: Routes to Second Malignancies in Young Patients.

SUMMARY: Given the rarity of cancer in childhood, it should be even more uncommon for pediatric cancer survivors to develop a second, independent malignancy, yet they incur a greatly elevated risk after initial remission. In this issue of Cancer Discovery, Sánchez-Guixé and colleagues unpick the origins of second tumours in four children, and the potential role platinum-based chemotherapy may play in subsequent tumorigenesis. See related article by Sánchez-Guixé et al., p. 953 (8).

Optimus-Era Dose Finding for Rare Cancers.

SUMMARY: Advances in cancer biology and diagnostics have led to the recognition of a multitude of rare cancer subtypes, emphasizing the pressing need for strategies to accelerate drug development for patients with these cancers. This paper addresses the unique challenges of dose finding in trials that accrue small numbers of patients with rare cancers; strategies for dose optimization are proposed, in line with evolving approaches to dose determination in the age of the US Food and Drug Administration's Project Optimus.

Cytotoxic and molecular differences of anticancer agents on 2D and 3D cell culture.

BACKGROUND: Cancer and multidrug resistance are regarded as concerns related to poor health outcomes. It was found that the monolayer of 2D cancer cell cultures lacks many important features compared to Multicellular Tumor Spheroids (MCTS) or 3D cell cultures which instead have the ability to mimic more closely the in vivo tumor microenvironment. This study aimed to produce 3D cell cultures from different cancer cell lines and to examine the cytotoxic activity of anticancer medications on both 2D and 3D systems, as well as to detect alterations in the expression of certain genes levels. METHOD: 3D cell culture was produced using 3D microtissue molds. The cytotoxic activities of colchicine, cisplatin, doxorubicin, and paclitaxel were tested on 2D and 3D cell culture systems obtained from different cell lines (A549, H1299, MCF-7, and DU-145). IC50 values were determined by MTT assay. In addition, gene expression levels of PIK3CA, AKT1, and PTEN were evaluated by qPCR. RESULTS: Similar cytotoxic activities were observed on both 3D and 2D cell cultures, however, higher concentrations of anticancer medications were needed for the 3D system. For instance, paclitaxel showed an IC50 of 6.234 µM and of 13.87 µM on 2D and 3D H1299 cell cultures, respectively. Gene expression of PIK3CA in H1299 cells also showed a higher fold change in 3D cell culture compared to 2D system upon treatment with doxorubicin. CONCLUSION: When compared to 2D cell cultures, the behavior of cells in the 3D system showed to be more resistant to anticancer treatments. Due to their shape, growth pattern, hypoxic core features, interaction between cells, biomarkers synthesis, and resistance to treatment penetration, the MCTS have the advantage of better simulating the in vivo tumor conditions. As a result, it is reasonable to conclude that 3D cell cultures may be a more promising model than the traditional 2D system, offering a better understanding of the in vivo molecular changes in response to different potential treatments and multidrug resistance development.

Rationally designed ß-cyclodextrin-crosslinked polyacrylamide hydrogels for cell spheroid formation and 3D tumor model construction.

In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of ß-cyclodextrin (ß-CD)-crosslinked polyacrylamide hydrogels with different ß-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of ß-CD-methacrylate (CD-MA) and a small amount of N,N'-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.

The Ottawa clinical fear of recurrence instruments: A screener, self-report, and clinical interview.

OBJECTIVE: Clinical fear of cancer recurrence (FCR) was recently defined by a group of experts during a Delphi study. Five criteria were agreed upon, namely: (a) high levels of preoccupation, (b) high levels of worry, (c) that are persistent, (d) hypervigilance and hypersensitivity to physical sensations that e) may result in functional impairment. No existing instruments comprehensively capture all these criteria for clinical FCR. METHODS: To remedy this gap, a set of three patient-reported outcome instruments including a one-item screener, self-report questionnaire, and semi-structured clinical interview, named the Ottawa Clinical Fear of Recurrence instruments, were developed. To do so, the research team first conducted a literature review of potential items. Additional FCR experts discussed the content of the screener and interview. The self-report's items were assessed for content validity by the same expert panel using Likert ratings and the Content Validity Index to narrow down the number of items. The three instruments were piloted with a group of cancer survivors to assess face validity following the European Organization for Research and Treatment of Cancer recommendations. RESULTS: The literature review and content validity assessment led to a final draft pre-pilot of 23 potential items for the self-report questionnaire. The instruments were piloted. Pilot study participants suggested changing wording and response options (particularly for the self-report) for greater clarity. CONCLUSIONS: Based on the feedback received, minor modifications were made, mostly for the self-report. In general, content and face validity for the three instruments were good for both experts and cancer survivors.

The scaffold protein disabled 2 (DAB2) and its role in tumor development and progression.

BACKGROUND: Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways. METHODS AND RESULTS: We conducted a comprehensive review of the literature focusing on the structure, expression, physiological functions, and tumor-suppressive roles of DAB2. We provide an overview of the structure, expression, and physiological functions of DAB2. Evidence supporting DAB2's role as a tumor suppressor is explored, highlighting its ability to inhibit cell proliferation, induce apoptosis, and modulate key signaling pathways involved in tumor suppression. The interaction between DAB2 and key oncogenes is examined, elucidating the interplay between DAB2 and oncogenic signaling pathways. We discuss the molecular mechanisms underlying DAB2-mediated tumor suppression, including its involvement in DNA damage response and repair, regulation of cell cycle progression and senescence, and modulation of epithelial-mesenchymal transition (EMT). The review explores the regulatory networks involving DAB2, covering post-translational modifications, interactions with other tumor suppressors, and integration within complex signaling networks. We also highlight the prognostic significance of DAB2 and its role in pre-clinical studies of tumor suppression. CONCLUSION: This review provides a comprehensive understanding of the molecular mechanisms by which DAB2 exerts its tumor-suppressive functions. It emphasizes the significance of DAB2 in cancer signaling pathways and its potential as a target for future therapeutic interventions.

Targeted Molecular Imaging and Therapy Based on Nuclear and Optical Technologies.

Both nuclear and optical imaging are used for in vivo molecular imaging. Nuclear imaging displays superior quantitativity, and it permits imaging in deep tissues. Thus, this method is widely used clinically. Conversely, because of the low permeability of visible to near-IR light in living animals, it is difficult to visualize deep tissues via optical imaging. However, the light at these wavelengths has no ionizing effect, and it can be used without any restrictions in terms of location. Furthermore, optical signals can be controlled in vivo to accomplish target-specific imaging. Nuclear medicine and phototherapy have also evolved to permit targeted-specific imaging. In targeted nuclear therapy, beta emitters are conventionally used, but alpha emitters have received significant attention recently. Concerning phototherapy, photoimmunotherapy with near-IR light was approved in Japan in 2020. In this article, target-specific imaging and molecular targeted therapy utilizing nuclear medicine and optical technologies are discussed.

OGA mutant aberrantly hydrolyzes O-GlcNAc modification from PDLIM7 to modulate p53 and cytoskeleton in promoting cancer cell malignancy.

O-GlcNAcase (OGA) is the only human enzyme that catalyzes the hydrolysis (deglycosylation) of O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation) from numerous protein substrates. OGA has broad implications in many challenging diseases including cancer. However, its role in cell malignancy remains mostly unclear. Here, we report that a cancer-derived point mutation on the OGA's noncatalytic stalk domain aberrantly modulates OGA interactome and substrate deglycosylation toward a specific set of proteins. Interestingly, our quantitative proteomic studies uncovered that the OGA stalk domain mutant preferentially deglycosylated protein substrates with +2 proline in the sequence relative to the O-GlcNAcylation site. One of the most dysregulated substrates is PDZ and LIM domain protein 7 (PDLIM7), which is associated with the tumor suppressor p53. We found that the aberrantly deglycosylated PDLIM7 suppressed p53 gene expression and accelerated p53 protein degradation by promoting the complex formation with E3 ubiquitin ligase MDM2. Moreover, deglycosylated PDLIM7 significantly up-regulated the actin-rich membrane protrusions on the cell surface, augmenting the cancer cell motility and aggressiveness. These findings revealed an important but previously unappreciated role of OGA's stalk domain in protein substrate recognition and functional modulation during malignant cell progression.

Exploring the reasons for wanting a peer partner to be physically active among women living with and beyond a cancer diagnosis: a content analysis.

BACKGROUND: Initiating and maintaining exercise is challenging for women during and post-cancer treatment. Adopting a peer partner model to provide social support to be active may contribute to lasting behaviour change of both partners. Despite this, finding a "like peer" can be challenging. PURPOSE: To explore women's reasons for seeking an online exercise partner following a diagnosis with cancer (through  www.activematch.ca ). We also examined women's potential sociodemographic and cancer-related differences by reported reasons for wanting an exercise partner. METHODS: Individuals creating an ActiveMatch profile completed demographic and physical activity questions (N = 199, Mage(SD) = 51.9(10.8) years), including an open-ended question regarding their "reason for wanting an exercise partner". An inductive content analysis was completed focusing on the participants' peer exercise partner preferences. Additional chi-square tests were run to assess whether participants differed based on sociodemographic and cancer-related characteristics and their motivations to be active by category of "reason for wanting an exercise partner" endorsed in the open-ended question. RESULTS: The participants' reasons for wanting an exercise partner were coded into seven categories, with most participants highlighting the reasons of motivation (52.3%), social support (48.7%), and accountability and adherence (26.6%). Women < 50 years of age were more likely to report accountability and adherence-related preferences for a partner. Those reporting endorsing weight loss as their primary reason for becoming active were more likely to be categorized as wanting a peer partner for motivation. CONCLUSIONS: While finding a peer partner can be challenging, matching women living with and beyond a cancer diagnosis based on their reason for wanting an exercise partner, as well as their reasons for wanting to be active, may be important to build successful peer exercise partnerships.