Cancer Disease Processes Research Articles

Quiescence-Origin Senescence: A New Paradigm in Cellular Aging.

Cellular senescence, traditionally viewed as a consequence of proliferating and growing cells overwhelmed by extensive stresses and damage, has long been recognized as a critical cellular aging mechanism. Recent research, however, has revealed a novel pathway termed "quiescence-origin senescence", where cells directly transition into senescence from the quiescent state, bypassing cell proliferation and growth. This opinion paper presents a framework conceptualizing a continuum between quiescence and senescence with quiescence deepening as a precursor to senescence entry. We explore the triggers and controllers of this process and discuss its biological implications. Given that the majority of cells in the human body are dormant rather than proliferative, understanding quiescence-origin senescence has significant implications for tissue homeostasis, aging, cancer, and various disease processes. The new paradigm in exploring this previously overlooked senescent cell population may reshape our intervention strategies for age-related diseases and tissue regeneration.

Neuro-ophthalmic complications of modern anti-cancer drugs

PurposeTargeted cancer therapies have been responsible for a dramatic shift in treatment strategies for cancer, and the number of drugs, classes, and indications are continually growing. Neuro-ophthalmic complications of these medications are an uncommon but important subset of adverse events which profoundly impact vision. This review aims to collate studies and reports of known neuro-ophthalmic complications of targeted therapies and describe their management.MethodsThe anti-cancer drugs included in the review were any drugs targeting specific molecules involved in the cancer disease process. PubMed, EMBASE, and Web of Science were searched using the generic names of each drug and keywords of neuro-ophthalmic conditions. The prescribing information published by the US Food and Drug Administration (FDA) for each drug was also reviewed.ResultsSeveral classes of targeted anti-cancer drugs were found to cause neuro-ophthalmic adverse effects. Immune checkpoint inhibitors are responsible for a raft of immune-related adverse events such as optic neuritis, ischemic optic neuropathy, PRES, and myasthenia gravis. Therapies with anti-VEGF activity can provoke posterior reversible leukoencephalopathy, which commonly presents with visual loss and can be fatal if not treated promptly. Inhibitors of BCR-ABL1, VEGF, ALK, and proteasomes have all been linked to optic nerve disorders which can have debilitating consequences for vision.ConclusionThe neuro-ophthalmic complications of modern anti-cancer drugs can limit or necessitate the withdrawal of these life-prolonging medications. Ophthalmologists should be alert for neuro-ophthalmic complications in these medications to facilitate prompt diagnosis and treatment and reduce the risk of severe and permanent consequences.

Study of Various Modalities of Management of Lower One-third Leg Defects in a Tertiary Care Hospital

Background: Lower extremity reconstruction is essential to plastic surgery and focuses on treating wounds and defects secondary to trauma, cancer, or chronic disease processes. Anatomical features of the lower third of the leg like subcutaneous bone surrounded by tendons with no muscles and vessels in isolated compartments with little intercommunication between them make the coverage of the wounds in the region a challenging problem. Aim: to study the various modalities of surgical management of lower 1/3rd leg defects. The study also aims to study the defect size and region in planning various flaps possible in the reconstruction ladder. Methods: The study was conducted from September 2014 to June 2017 on patients admitted to the Department of Burns, Plastic & Reconstructive Surgery and referred patients from the Department of General Surgery & Orthopaedic Surgery, S C B Medical College & Hospital, Cuttack. The Study includes all lower 3rd Leg defect varieties for different surgical treatment modalities. Results: Various reconstructive methods were used to cover the lower 1/3rdleg defects; the maximum was the free muscle transfer in 9 cases. The following typical flap used was the reverse sural flap. Conclusion: The goal in lower limb reconstruction involves needing a stable skeleton, allowing weight-bearing status, with adequate soft tissue coverage to nourish and protect the underlying bone. What one would use for reconstruction depends upon the surgeon’s familiarity and comfort levels with the technique as much as the various circumstances.

Pain associated with breast cancer: etiologies and therapies.

Pain associated with breast cancer is a prevalent problem that negatively affects quality of life. Breast cancer pain is not limited to the disease course itself but is also induced by current therapeutic strategies. This, combined with the increasing number of patients living with breast cancer, make pain management for breast cancer patients an increasingly important area of research. This narrative review presents a summary of pain associated with breast cancer, including pain related to the cancer disease process itself and pain associated with current therapeutic modalities including radiation, chemotherapy, immunotherapy, and surgery. Current pain management techniques, their limitations, and novel analgesic strategies are also discussed.

Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer

SIWA318H is a novel monoclonal antibody that selectively targets an advanced glycation end product biomarker found in damaged/dysfunctional cells exhibiting (a) aerobic glycolysis, and (b) oxidative stress. Cells with this biomarker are dysfunctional and are associated with stresses and/or damages relating to aging, cancer and other disease processes. In this study, we evaluated the biological effects and antitumor activity of SIWA318H in preclinical models for pancreatic cancer. SIWA318H binds to pancreatic cancer cells and cancer-associated fibroblasts, as well as tumor xenografts derived from pancreatic cancer patients. Furthermore, SIWA318H induced significant antibody-dependent cell-mediated cytotoxicity (ADCC) against pancreatic cancer cells. In a humanized CD34+ NSG mouse xenograft model for pancreatic cancer, tumors in mice treated with SIWA318H grew significantly slower compared to those in control mice (p < 0.001). After 3 weeks of treatment with SIWA318H, the tumor growth was suppressed by 68.8% and 61.5% for the high and low dose regimens, respectively, when compared to the isotype antibody control (ANOVA p < 0.002). Moreover, a significant increase in complete remission (CR) rate was observed in mice receiving the high dose (60%, p < 0.04) or low dose (77.8%, p < 0.02) of SIWA318H treatment compared with control mice (6.7%). Immunohistochemical analyses of the tumor tissues showed a significant decrease in senescent cells in the tumor microenvironment of SIWA318H treated mice compared to that of control treated mice (p < 0.05). These results provide compelling evidence that SIWA318H is a promising novel therapeutic against pancreatic cancer.

Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer

T cell leukemia homeobox 2 (TLX2) plays an important role in some tumors. Bioinformatics and experimental validation represent a useful way to explore the mechanisms and functions of TLX2 gene in the cancer disease process from a pan cancer perspective. TLX2 was aberrantly expressed in pan cancer and cell lines and correlated with clinical stage. High TLX2 expression was significantly associated with poor overall survival in COAD, KIRC, OC, and UCS. The greatest frequency of TLX2 alterations in pan cancer was amplification. Alterations of NXF2B, MSLNL, PCGF1, INO80B-WBP1, LBX2-AS1, MRPL53, LBX2, TTC31, WDR54, and WBP1 co-occurred in the TLX2 alteration group. PFS was significantly shorter in the TLX2-altered group (n = 6) compared to the TLX2-unaltered group (n = 400). Methylation levels of TLX2 were high in 17 tumors. TLX2 expression was associated with MSI in seven tumors and TMB in five tumors. TLX2 expression was associated with immune infiltration and immune checkpoint genes. TLX2 may be associated with some pathways and chemoresistance. We constructed a possible competing endogenous RNA (ceRNA) network of LINC01010/miR-146a-5p/TLX2 in OC. TLX2 expression was significantly upregulated in ovarian cancer cell lines compared to ovarian epithelial cell lines. Aberrant expression of TLX2 in pan cancer may promote tumorigenesis and progression through different mechanisms. TLX2 may represent an important therapeutic target for human cancers.

VELscope: The challenge for the detection of orally potentially malignant lesions

Early detection of oral cancer is crucial in improving survival rate; Identification and detection of oral potentially malignant disorders (OPMD) allow delivery of interventions to reduce the evolution of these disorders to malignancy. A variety of new and emerging diagnostic aids and adjunctive techniques are currently available to potentially assist in the detection of OPMD such as the autofluorescence technique.Pathologists utilize the autofluorescence approach to investigate body mucosa and screen for changes in tissue, which could lead to the earlier detection of pre-malignant, cancer, or other disease processes. Early identification is the most effective way to ensure treatment effectiveness, boost survival rates, and maintain a high quality of life. Autofluorescence examination of oral tissues using the VELscope has suggested as an adjunctive tool for cancer detection and diagnosis. The aim of our study was to evaluate the efficacy of the VELscope system autofluorescence to image the tissue of potentially malignant oral lesions. Also, to assess the diagnostic accuracy, sensitivity and specificity of this method.

Prevention over screening for ovarian cancer in patients with high-risk germline mutations: Misinterpreting the findings of ALDO

In November 2022, the findings of the Avoiding Late Diagnosis of Ovarian cancer (ALDO) study were published. Subsequent media coverage suggested that investigators had found a safe alternative to risk-reducing bilateral salpingoophorectomy (rrBSO) in patients with pathogenic BRCA1 and BRCA2 germline mutations who chose to decline or defer risk-reducing surgery. Unfortunately, this media coverage was largely misleading. Specifically, in the ALDO trial, 4 of 6 patients found to have ovarian cancer by the ALDO screening methodology were diagnosed with advanced-stage disease. The primary endpoint of the ALDO study was the rate of complete surgical cytoreduction, rather than stage at diagnosis or overall survival, which is an inappropriate surrogate for benefit in a population at risk of ovarian cancer.The ALDO trial again demonstrates that screening women at high-risk of ovarian cancer should not be considered a safe alternative to risk-reducing surgery, and can lead to false reassurance and the development of preventable cases of ovarian cancer. While we should continue to investigate new screening options, future efforts should largely focus on why patients decline rrBSO in the first place and how we can pivot our efforts to better address concerns related to rrBSO, including sequelae of surgical menopause. Furthermore, as we continue to understand the role of the fallopian tube in the epithelial ovarian cancer (EOC) disease process, we must identify the role of salpingectomy alone in prevention of EOC.

Activity-Based Imaging of Macrophage Migration Inhibitory Factor with a Two-Photon Fluorescent Probe.

Macrophage migration inhibitory factor (MIF), as a cytokine, plays an important role in the pathogenesis of cancer and some other diseases, and it is also one of the potential drug targets for disease treatment. However, due to the lack of simple and effective MIF imaging detection tools, the fluctuation and distribution of MIF in living cells or at lesion sites remain difficult to track precisely and in real time. Here, we report activity-based fluorescent probes, named MIFP1-MIFP3, which are used for real-time imaging and tracking of intracellular MIF, thus establishing a relationship between the fluctuation of MIF and the change of fluorescence signal during the cancer disease process. With the excellent optical properties of two-photon probe imaging, we can easily distinguish multiple cancer cells from normal cells with the representative probe, MIFP3. Moreover, MIFP3 has also been successfully used to directly identify the pathological tissues of patients with clinical liver cancer. These potential MIF probes could provide powerful tools for further study of the physiological function of MIF and will be helpful to promote the accurate diagnosis and therapeutic evaluation of MIF-associated malignancies.

Potential of nuclear magnetic resonance metabolomics in the study of prostate cancer.

Nuclear magnetic resonance (NMR) metabolomics is a powerful analytical technique and a tool which has unique characteristics and capabilities for the evaluation of a number of biochemicals/metabolites of cancer and other disease processes that are present in biofluids (urine and blood) and tissues. The potential of NMR metabolomics in prostate cancer (PCa) has been explored by researchers and its usefulness has been documented. A large number of metabolites such as citrate, choline, and sarcosine were detected by NMR metabolomics from biofluids and tissues related to PCa and their levels were compared with controls and benign prostatic hyperplasia. The changes in the levels of these metabolites aid in the diagnosis and help to understand the dysregulated metabolic pathways in PCa. We review recent studies on in vitro and ex vivo NMR spectroscopy-based PCa metabolomics and its possible role as a diagnostic tool.

Experience of childhood cancer: A narrative inquiry.

To more fully understand the possible impact of childhood cancer on a young person's life through their own story. Using Connelly and Clandinin's narrative inquiry method, a participant named Noelle was engaged in a series of narrative interviews and a creative self-expression activity about her cancer experience when she was 12. Her story was examined through the three-dimensional space of experience (person, place, and time), and analyzed using Erikson's Psychosocial Stages of Development framework theoretical lens. Two significant narrative patterns emerged: identity and relationships. Although the physical effects of the cancer were successfully treated, the impact of this disease impacted Noelle's own psychosocial development as she was trying to evolve her relationships with peers and family, while grappling with her new identity as a cancer patient. Healthcare professionals need to intentionally increase their sensitivity to adolescent patients' lived experience of cancer. More specifically, there is a need for further education of healthcare professionals on the psychosocial impact of cancer in both the immediate and long-term trajectory of the cancer disease process.

Structural Neuroimaging Findings Related to Adult Non-CNS Cancer and Treatment: Review, Integration, and Implications for Treatment of Cognitive Dysfunction.

Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.

Estimation of Aggregate Losses of Secondary Cancer Using PH-OPPL and PH-TPPL Distributions

Kenyan insurance firms have introduced insurance policies of chronic illnesses like cancer; however, they have faced a huge challenge in the pricing of these policies as cancer can transit into different stages, which consequently leads to variation in the cost of treatment. This has made the estimation of aggregate losses of diseases which have multiple stages of transitions such as cancer, an area of interest of many insurance firms. Mixture phase type distributions can be used to solve this setback as they can in-cooperate the transition in the estimation of claim frequency while also in-cooperating the heterogeneity aspect of claim data. In this paper, we estimate the aggregate losses of secondary cancer cases in Kenya using mixture phase type Poisson Lindley distributions. Phase type (PH) distributions for one and two parameter Poisson Lindley are developed as well their compound distributions. The matrix parameters of the PH distributions are estimated using continuous Chapman Kolmogorov equations as the disease process of cancer is continuous while severity is modeled using Pareto, Generalized Pareto and Weibull distributions. This study shows that aggregate losses for Kenyan data are best estimated using PH-OPPL-Weibull model in the case of PH-OPPL distribution models and PH-TPPL-Generalized Pareto model in the case of PH-TPPL distribution models. Comparing the two best models, PH-OPPL-Weibull model provided the best fit for secondary cancer cases in Kenya. This model is also recommended for different diseases which are dynamic in nature like cancer.

The science of hope.

Hope is a contextual term that has different connotations depending on the setting. We analyse the concept of hope with respect to its applicability for oncology. We review studies that present hope as a direct or secondary mediator of outcome. We posit that an individual's level of hope is often determined by innate personality characteristics and environmental factors, but can also be physiologically influenced by immune modulators, neurotransmitters, affective states, and even the underlying disease process of cancer. We argue that hope can be a therapeutic target and review evidence showing the effects of hope-enhancing therapies. Given the potential for hope to alter oncological outcomes in patients with cancer and the opportunity for improvement in quality of life, we suggest further research directions in this area.

PCN146 COST-EFFECTIVENESS ANALYSIS OF ANLOTINIB AS A THIRD-LINE OR FURTHER TREATMENT IN ADVANCED NON-SMALL LUNG CANCER

Anlotinib, a novel multitarget tyrosine kinase inhibitor, has revealed the significant efficacy compared with placebo in advanced non-small lung cancer. We aimed to assess the cost-effectiveness of anlotinib as the third-line and further therapy for this population from the Chinese payer perspective. A Markov model was performed to simulate the disease process of advanced non-small lung cancer in three states: progression-free survival (PFS), progressive disease (PD), and death. The major clinical information was derived from the ALTER 0303 trial. Cost data were calculated from the perspective of the Chinese healthcare payer. Parameters uncertainties were explored by one-way sensitivity analysis and probabilistic sensitivity analysis. Anlotinib cost $12,759.84 and yielded a survival of 0.34 QALY, while the placebo cost $3,799.80 and yielded a survival of 0.26 QALY. Therefore, the incremental cost-effectiveness ratio of anlotinib versus placebo was $112,000.5 which surpassed the willingness-to-pay threshold in China. The most influential factors of the model were utility of PFS state and the cost of anlotinib. Anlotinib is not a cost-effective regimen as the third-line and later treatment for the patients with advanced non-small cell lung cancer from the Chinese societal perspective.

Diagnosis of gastric cancer by MDCT gastrography: diagnostic characteristics and management potential

BackgroundGastric cancer is regarded as the fifth most frequent tumor globally but the third most common fatal illness. As early as possible, we diagnose cancer stomach especially at early stages, the higher the rate of life. Nevertheless, most cases are diagnosed at late cases where surgery is not of the same benefit at early stages because of clinically indefinite symptoms. The prospective study goal is to estimate the role of MDCT in diagnosis and staging of cancer stomach.ResultsIn our study, it was found that there was a high relationship between pathological and CT staging by using MPR. CT with MPR was specific and accurate in diagnosis of all stages of gastric cancer with specificity ranged between 93 and 97% and accuracy ranged between 90 and 92.5%. However, it showed lowest sensitivity in diagnosis of stage 1 of gastric cancer. On the other hand, it showed highest sensitivity (90%) in diagnosis of stage IV as well as we found that MPR and VR of MDCT are much more accurate (92.5%) than multi-detector computed tomography axial images (80%) in the diagnosis of all stages of gastric cancer with the difference between the two sequences was significant (P = 0.009).ConclusionOur results demonstrate that preoperative MDCT with contrast filling technique for abdomen and pelvis evaluates the local disease process of gastric cancer as well as the potential areas of spread. This information is vital in choosing between palliative or radical surgery. MPR and VR help in the assessment of tumor extension and considered as a highly representative prognostic value. Making it the imaging modality of choice in diagnosis and staging of gastric cancers.

Percutaneous palliative care interventions in the cancer patient.

Patients with incurable cancer face lots of problems before they expire. Complications resulting from cancer or its treatment are a significant determinant of the quality of life of cancer patients. It is of outmost importance to make use of all treatment options in order to improve their survival and quality of life. Nowadays, available are a number of Interventional Radiology procedures that are minimally invasive, can be performed under local anesthesia or conscious sedation and are indispensable in helping patient through the cancer disease process. These techniques can be broadly classified into drainage of fluid collections, decompression and relief of obstruction, pain and tumor burden reduction, vascular and gastrointestinal tract access as well as hemostasis. The purpose of this article is to describe the basic concepts of minimally invasive techniques applied as palliative care therapies in the cancer patients. Controversies concerning techniques and products and the need for patient-centered tailored approaches will be discussed.

REPRESENTAÇÕES SOCIAIS DE ADOLESCENTES SOBRE O PROCESSO DE ADOECER E ADOLESCER COM CÂNCER

Objetivo: descrever as representações sociais de adolescentes sobre o processo de adoecimentode câncer.Método: estudo descritivo, com abordagem qualitativa, embasado na Teoria das RepresentaçõesSociais, com 31 adolescentes em tratamento oncológico em um hospital público, em Belém doPará. Realizado com entrevistas individuais, submetidas à análise temática indutiva.Resultados: identificaram-se três categorias temáticas: o câncer como doença psicossocial; avivência do adoecer e adolescer com câncer; e o enfrentamento das alterações corporais advindasdo adoecimento.Conclusão: o estudo contribuiu para a compreensão das representações sociais sobre o câncer naadolescência, subsidiando o enfermeiro na construção de conhecimentos junto ao adolescentecom câncer, para assistência de maior qualidade.

S-1 or gemcitabine adjuvant therapy in resected pancreatic cancer: a cost-effectiveness analysis based on the JASPAC-01 trial

ABSTRACT Purpose This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer. Methods A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty. Results Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters. Conclusion Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

Early Diagnosis on Oral and Potentially Oral Malignant Lesions: A Systematic Review on the VELscope® Fluorescence Method.

The fluorescence method is an innovative technique used by pathologists for examining body mucosa, and for the abnormalities tissue screening, potentially leading to the earlier discovery of pre-cancer, cancer or other disease processes. The early detection is one of the best mechanisms for enabling treatment success, increasing survival rates and maintaining a high quality of life. The purpose of this review is to evaluate the clinical efficiency of this diagnostic tool applied to the oral cavity (VELscope®). A literature systematic review has been performed. The initial research provided 53 results after applying the inclusion and exclusion criteria, and after a manual screening of the abstracts by the authors, only 25 results were eligible for review. The results and data contained in all the researches, no older than 10 years, were manually evaluated, and provided useful information on this diagnostic method. The VELscope® mean value about sensitivity and specificity resulted of 70.19% and 65.95%, respectively, by results analysis, but despite this some studies disagree about its clinical effectiveness, and this diagnostic method is still much debated in scientific and clinical medical literature. Surely being able to have efficient and effective tools from this point of view could help the clinician in the diagnosis, and also make timelier the pharmacological or surgical therapy, improving the quality of life of the patient, and in some cases guaranteeing a longer survival term.