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Background: This paper aimed to explore the palliative care (PC) needs and barriers to access among cancer patients in a rural region of North India with a high cancer burden., Methods: A Participatory action research (PAR) approach was employed. Situational assessment, community sensitization workshops (CSWs) and door-to-door surveys were planned, conducted and developed over three PAR cycles. A parallel convergent mixed-methods approach was adopted wherein the quantitative data from door-to-door surveys and qualitative data from CSWs and investigator field notes were collected and analyzed to provide a comprehensive understanding of PC needs and barriers to access. Descriptive statistics and thematic analysis were used., Results: A total of 27 CSWs involving 526 stakeholders were conducted. A total of 256 cancer patients were assessed for PC needs and symptom burden using the Supportive and Palliative Care Indicators (SPICT-4ALL) and the Edmonton Symptom Assessment System (ESAS) tool, respectively. Based on the SPICT assessment, all patients (n = 256) satisfied general and/or cancer-specific indicators for PC. The majority (56.6%) had ≥ one moderate-severe symptom, with the most common symptoms being tiredness, pain and loss of appetite. Analysis of qualitative findings generated three themes: unmet needs, burden of caregiving, and barriers and challenges. Cancer affected all domains of patients' and their families' lives, contributing to biopsychosocial suffering. Social stigma, discrimination, sympathizing attitudes and lack of emotional and material support contributed to psychosocial suffering among cancer patients and their caregivers. Lack of awareness, nearby healthcare facilities, transportation, essential medicines, trained manpower and education in PC, collusion, fear of social discrimination, faulty perceptions and misconceptions about cancer made access to PC difficult., Conclusions: The study emphasize the need for and provide a roadmap for developing context-specific and culturally appropriate CBPC services to address the identified challenges and needs. The findings point towards education of CHWs in PC; improving community awareness about cancer, PC, government support schemes; ensuring an uninterrupted supply of essential medicines; and developing active linkages within the community and with NGOs to address the financial, transportation, educational, vocational and other social needs as some of the strategies to ensure holistic CBPC services., Trial Registration: Clinical Trial Registry of India (CTRI/2023/04/051357)., (© 2024. The Author(s).)

This study conducts the first meta-analysis to assess the aggregated risk of malignancy associated with each category of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) for reporting serous effusion cytology, while also evaluating diagnostic accuracy. PubMed/MEDLINE and Embase were systematically searched using the keywords "(pleural, peritoneal, and pericardial effusions) AND (serous effusion cytology) OR (International System for Reporting Serous Fluid Cytopathology)". Articles underwent risk of bias assessment using the QUADAS-2 tool. After excluding inadequate samples, a meta-analysis determined sensitivity and specificity for different cutoff points, including "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive." Summary receiver operating characteristic curves assessed diagnostic accuracy, and the diagnostic odds ratio was pooled. Sixteen retrospective cross-sectional studies, totaling 19,128 cases, were included. Sensitivity and specificity for the "atypical and higher risk categories" considered positive were 77% (95% confidence interval [CI], 68%-84%) and 95% (95% CI, 93%-97%) respectively. For the "suspicious for malignancy and higher risk categories" considered positive, sensitivity and specificity were 57% (95% CI, 49%-65%) and 100% (95% CI, 99%-100%) respectively. Sensitivity and specificity for the "malignant" category considered positive for malignancy were 70% (95% CI, 60%-77%) and 99% (95% CI, 98%-99%), respectively. The pooled area under the curve ranged from 85% to 89.5% for each cutoff. This meta-analysis underscores the ISRSFC's accuracy in reporting serous fluid cytology. It emphasizes the diagnostic importance of the "suspicious" and "malignant" categories in identifying malignancy, and the role of the "benign" category in ruling out malignancy., (© 2024 American Cancer Society.)

The global demographic and epidemiological transition have led to a rapidly increasing burden of cancer, particularly among older adults. There are scant data on the prevalence and demographic pattern of cancer in older Indian persons. This was a multicentric observational study conducted between January 2019 and December 2020. Data were retrieved from existing electronic databases to gather information on two key variables: the total number of patients registered with oncologists and the number of patients aged 60 years and above. The primary objective was to determine the percentage of older adults among patients with cancer served by these hospitals. Secondary objectives included understanding the prevalence of different types of cancer in the older population, and the sex- and geographic distribution of cancer in older Indian patients. We included 272,488 patients with cancer from 17 institutes across India. Among them, 97,962 individuals (36 %) were aged 60 years and above. The proportion of older adults varied between 20.6 % and 53.6 % across the participating institutes. The median age of the older patients with cancer was 67 (interquartile range, 63-72) years. Of the 54,281 patients for whom the details regarding sex were available, 32,243 (59.4 %) were male. Of the 56,903 older patients, head and neck malignancies were the most prevalent, accounting for 11,158 cases (19.6 %), followed by breast cancer (6260 cases, 11 %), genitourinary cancers (6242 cases, 10.9 %), lung cancers (6082 cases, 10.7 %), hepatopancreaticobiliary (6074, 10.7 %), and hematological malignancies (5226 cases, 9.2 %). Over one-third of Indian patients with cancer are aged 60 years and above, with a male predominance. Head and neck, breast, and genitourinary cancers are the most prevalent in this age group. Characterizing the burden of cancer in older adults is crucial to enable tailored interventions and additional research to improve the care and support for this vulnerable population., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest from any authors associated with this publication. No funding was required for this project., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies., Methods: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics., Results: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China., Conclusions: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk., (© 2024. The Author(s).)

Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To explore the magnitude of sex bias and determinants of treatment abandonment (TA) in childhood cancer in India., Methods: Individual data of children (0-19 y) registered between January 1, 2017 and July 31, 2022, was compiled. TA was defined as defaulting curative intent treatment ≥4 wk. Defaulting treatment irrespective of intent ≥4 wk was defined as Treatment Default (TD). The primary outcome was the proportion of male-to-female children with TA. Secondary outcomes included the proportion of male-to-female children with upfront TA, TA at relapse, TD, TD-p (TD only in the palliative setting). The impact of clinico-demographic factors on TA was analysed using multivariable regression and propensity score matching (PSM)., Results: Three thousand two hundred eighty four patients were analysed. The overall male-to-female ratio (MFR) was 2.08 (95% CI 1.94-2.24). Of 2906 patients treated with curative intent, 415 (14·3%) abandoned treatment. TA was higher in females than males (16·4% vs. 13·3%; p = 0·022) with adjusted MFR of 0·81 (0·66-0·98). The adjusted MFR of TA for treatment-naïve and relapsed patients and TD were 0·73 (0·59-0·91), 1·13 (0·65-1·96) and 0·84 (0·71-1·00) respectively. Sex independently predicted TA on multivariable analysis. However, on PSM analysis including socio-economic variables, lower maternal education predicted higher TA in children with cancer (10·1% vs. 6%, p = 0·015)., Conclusions: Child sex predicted TA in childhood cancer in India with more females abandoning treatment. Maternal education is a more crucial factor predicting TA over child sex, when socio-economic factors were considered. Hence, policies promoting female education and gender equality may mitigate sex-based gaps in childhood cancer care., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Introduction: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India., Methodology: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility., Results: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction)., Conclusion: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India., Plain Language Summary: In India, the number of eligible patients benefiting from high-precision particle therapy technology is projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach., (© 2024 American Cancer Society.)

Despite many efforts, a comprehensive understanding and clarification of the intricate connections within cancer cell metabolism remain elusive. This might pertain to intracellular dynamics and the complex interplay between cancer cells, and cells with the tumor stroma. Almost a century ago, Otto Warburg found that cancer cells exhibit a glycolytic phenotype, which continues to be a subject of thorough investigation. Past and ongoing investigations have demonstrated intricate mechanisms by which tumors modulate their functionality by utilizing extracellular glucose as a substrate, thereby sustaining the essential proliferation of cancer cells. This concept of "aerobic glycolysis," where cancer cells (even in the presence of enough oxygen) metabolize glucose to produce lactate plays a critical role in cancer progression and is regulated by various signaling pathways. Recent research has revealed that the canonical wingless-related integrated site (WNT) pathway promotes aerobic glycolysis, directly and indirectly, thereby influencing cancer development and progression. The present review seeks to gather knowledge about how the WNT/β-catenin pathway influences aerobic glycolysis, referring to relevant studies in different types of cancer. Furthermore, we propose the concept of impeding the glycolytic phenotype of tumors by employing specific inhibitors that target WNT/β-catenin signaling., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Mitochondria are one of the major sources of energy as well as regulators of cancer cell metabolism. Thus, they are potential targets for the effective treatment and management of cancer. Research has explored triphenylphosphonium (TPP) derivatives as potent cancer-targeting ligands because of their lipophilic nature and mitochondrial affinity. In this review, we summarize the utility of TPP-based conjugates targeting mitochondria in different types of cancer and other diseases, such as neurodegenerative and cardiovascular disorders. Such conjugates offer versatile therapeutic potential by modulating membrane potential, influencing reactive oxygen species (ROS) production, and coupling of molecular modifications (such as ATP metabolism and energy metabolism). Thus, we highlight TPP conjugates as promising mitochondria-targeting agents for use in targeted drug delivery systems., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

The PD-1/PD-L1 pathway plays a significant role in inhibiting, escaping from immune response, and promoting self-tolerance of the tumour. Dostarlimab is a selective humanized monoclonal antibody designed to target PD-1 and block its activity with PD-L1, which further prevents the escape of tumour cells from immune surveillance. It got accelerated approval from the FDA for treating adults with mismatch repair deficient, recurrent, or advanced endometrial cancer, and studies confirmed its beneficial effects. A recently published clinical trial reported 100 % remission of advanced rectal cancer without significant side effects in the participants. This clinical trial is still going on and enrolling patients with different types of cancer, including ovarian cancer, melanoma, head and neck cancer, and breast cancer therapy. The clinical trial result gave hope and proof to the medical fraternity and patients for better treatment. The focus of this review is to summarise pre-clinical and clinical studies of Dostarlimab., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I 2  = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I 2  = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I 2  = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I 2  = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Data on SARS-CoV-2 vaccine responsiveness in adolescent/young adult (AYA) cancer patients are sparse. The present study assessed humoral and cellular immune responses post-vaccination in this population., Methods: In this prospective study, patients aged 12-30 years undergoing cancer therapy ("on therapy") and survivors ("off therapy") were recruited. Anti-receptor binding domain (RBD) protein IgG levels were measured at baseline, four weeks post-first vaccine dose (T1), and six weeks post-second dose (T2). Cellular immunity was assessed using activation-induced markers and intracellular cytokine staining in a patient subset. The primary outcome was to quantify humoral responses in both cohorts at T2 compared to baseline. Clinical predictors of log antibody titres at T2 were identified., Results: Between April-December 2022, 118 patients were recruited of median age 15.4 years. Among them, 77 (65.2 %) were in the "on therapy" group, and 77 (65.2 %) had received the BBV152 vaccine. At baseline, 108 (91.5 %) patients were seropositive for anti-RBD antibody. The log anti-RBD titre rose from baseline to T2 (p-value = 0.001) in the whole cohort; this rise was significant from baseline-T1 (p-value < 0.001), but not from T1 to T2 (p-value = 0.842). A similar pattern was seen in the "on therapy" cohort. BECOV-2 vaccine was independently associated with higher log anti-RBD titres than BBV152 (regression coefficient: 0.41; 95 % CI: 0.10-0.73; p = 0.011). Cellular immune responses were similar in the "on-" and "off therapy" groups at the three time points., Conclusion: Among AYA cancer patients, a single non-mRNA vaccine dose confers robust hybrid humoral immunity with limited benefit from a second dose., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT., Methods: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation., Results: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2., Conclusion: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The proportion of childhood cancer survivors (CCS) in low/middle-income countries (LMICs) is rising. CCS often develop several physical and psycho-social long-term adverse effects, with unique healthcare needs. Primary healthcare providers (primary care physicians (PCPs)), especially in LMICs, are often not equipped to handle survivorship care. This study aimed to assess knowledge, and attitude among trainee healthcare providers concerning major issues of paediatric survivorship care., Methods: A multi-centre, cross-sectional, questionnaire-based study was conducted among nursing and medical undergraduate students, and postgraduate medical residents across three tertiary-care teaching hospitals in India-All India Institute of Medical Sciences, New Delhi; Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry; and Maulana Azad Medical College, New Delhi. A questionnaire with total of 24 questions (14 knowledge-based and 10 attitude-based) was finalised after validation by expert review and piloting. The major domains covered in the questionnaire included knowledge and attitude regarding long-term adverse effects and psychosocial, employment-related issues faced by the survivors. It was administered to the study participants electronically. The knowledge-based questions had true/false responses (scored as 0 or 1 if incorrect or correct, respectively). Attitude-based questions were scored as 5-point Likert scale., Results: Total 898 responses were collected (median age: 21 years, 64% (576/898) female). Among the respondents, 44% were undergraduate medical students, 42% were nursing students and 14% were postgraduate medical residents. The mean (SD) of knowledge score was 8.72 (2.04) (out of 14). On multivariable analysis, only discipline of training predicted knowledge scores regarding survivorship care. Postgraduate medical residents (9.08) as well as undergraduate medical students (8.85), had significantly higher mean knowledge scores than nursing students (8.47) (p=0.004).Two questions were answered incorrectly by the majority; children and siblings of CCS need additional genetic screening (79% incorrectly answered true), and CCS face intimacy issues in relation to normal sexual functioning (59% incorrectly answered false).Nearly half (48%) of respondents believed that their knowledge of cancer survivorship issues was inadequate. Majority of respondents (84%) suggested that oncologists should handle long-term survivorship care rather than PCPs., Conclusion: Trainee healthcare providers in India reported inadequate knowledge regarding survivorship care. Improving awareness by incorporating survivorship in teaching curriculum is imperative to equip future PCPs to provide survivorship care across the country., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Noncommunicable diseases (NCDs) contribute significantly to global morbidity and mortality, with cancer being one of the leading causes. In this prospective observational study, we aimed to investigate the prevalence and impact of endocrine disorders, specifically diabetes and thyroid dysfunction, in patients with advanced metastatic cancer undergoing cancer-directed therapy., Methods: Over 15 months, we recruited 100 histologically proven advanced metastatic cancer patients from the Department of Medical Oncology Haematology, All India Institute of Medical Sciences, Rishikesh, and conducted institutional-based prospective observational study. All participants over 18 years of age, treatment-naive, and potential candidates for systemic chemotherapy with an expected clinical survival of at least 6 months were included in the study. Patients with prior therapy, secondary neoplasms, and those unable to complete 3 months of palliative chemotherapy were excluded. Patients were assessed for diabetes and thyroid function at presentation, after 3 and 6 months of cancer-directed standard therapy. These data were analyzed, processed, and presented as results., Results: The mean age of participants was 50.45 years, with a near-equal distribution of males and females. At baseline, 10% of the study population had preexisting endocrine disorders (2% hypothyroidism, 8% diabetes). By the end of 6 months, the prevalence increased to 18%, with females being more affected. Notably, the prevalence of new-onset endocrine disorders during cancer-directed therapy was only 3% for diabetes and 4% for thyroid dysfunction., Conclusion: Analysis of sociodemographic and cancer-related characteristics showed no significant association with changes in diabetic and thyroid status at 3 and 6 months. However, substance use, particularly smoking, was associated with an increased risk of diabetes development (p < .05). Cancer type and treatment regimen did not show statistically significant correlations with endocrine dysfunction., Implications: Our study highlights the importance of considering endocrine disorders in advanced metastatic cancer patients undergoing therapy. The prevalence of diabetes and thyroid dysfunction increased during cancer-directed therapy, particularly in females. Careful monitoring and timely intervention are essential to improve the quality of life for these patients. Further research is warranted to explore the long-term effects of cancer-directed therapy on endocrine health and develop tailored management strategies for this vulnerable population., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Aurora kinases (AURKs) are a family of serine /threonine protein kinases that have a crucial role in cell cycle process mainly in the event of chromosomal segregation, centrosome maturation and cytokinesis. The family consists of three members including Aurora kinase A (AURK-A), Aurora kinase B (AURK-B) and Aurora kinase C (AURK-C). All AURKs contain a conserved kinase domain for their activity but differ in their cellular localization and functions. AURK-A and AURK-B are expressed mainly in somatic cells while the expression of AURK-C is limited to germ cells. AURK-A promotes G2 to M transition of cell cycle by controlling centrosome maturation and mitotic spindle assembly. AURK-B and AURK-C form the chromosome passenger complex (CPC) that ensures proper chromosomal alignments and segregation. Aberrant expression of AURK-A and AURK-B has been detected in several solid tumours and malignancies. Hence, they have become an attractive therapeutic target against cancer. The first part of this review focuses on AURKs structure, functions, subcellular localization, and their role in tumorigenesis. The review also highlights the functional and clinical impact of selective as well as pan kinase inhibitors. Currently, >60 compounds that target AURKs are in preclinical and clinical studies. The drawbacks of existing inhibitors like selectivity, drug resistance and toxicity have also been addressed. Since, majority of inhibitors are Aurora kinase inhibitor (AKI) type-1 that bind to the active (DFG in and C in ) conformation of the kinase, this information may be utilized to design highly selective kinase inhibitors that can be combined with other therapeutic agents for better clinical outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A tumor microenvironment often presents altered physicochemical characteristics of the extracellular matrix (ECM) including changes in matrix composition, stiffness, protein expression, pH, temperature, or the presence of certain stromal and immune cells. Of these, overexpression of matrix metalloproteinases (MMPs) and extracellular acidosis are the two major hallmarks of cancer that can be exploited for tumor detection. The change in matrix stiffness and the release of certain cytokines (TNF-α) in the tumor microenvironment play major roles in inducing MMP-9 expression in cancerous cells. This study highlights the role of mechanical cues in upregulating MMP-9 expression in cancerous cells using stiffness-tunable matrix compositions and dual-sensitive fluorescent nanoprobes. Ionically cross-linked 3D alginate/gelatin (AG) scaffolds with three stiffnesses were chosen to reflect the ECM stiffnesses corresponding to healthy and pathological tissues. Moreover, a dual-sensitive nanoprobe, an MMP-sensitive peptide conjugated to carbon nanoparticles with intrinsic pH fluorescence properties, was utilized for in situ monitoring of the two cancer hallmarks in the 3D scaffolds. This platform was further utilized for designing a 3D core-shell platform for spatially mapping tumor margins and for visualizing TNF-α-induced MMP-9 expression in cancerous cells.

Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved molecular and metabolomic understanding of various diseases, including cancer. In addition, three-dimensional (3-D) disease models have been efficiently utilized for understanding disease pathophysiology and as screening tools in drug discovery. An integrated approach utilizing pan-omics technologies and 3-D in vitro tumor models has led to improved understanding of the intricate network encompassing various signalling pathways and molecular cross-talk in solid tumors. In the present review, we underscore the current trends in omics technologies and highlight their role in understanding genotypic-phenotypic co-relation in cancer with respect to 3-D in vitro tumor models. We further discuss the challenges associated with omics technologies and provide our outlook on the future applications of these technologies in drug discovery and precision medicine for improved management of cancer., (© 2024. The Author(s).)

Introduction: The Sustainable Development Goals of the United Nations include a commitment to "leave no one behind" as a universal goal. To achieve this in geriatric oncology (GO) worldwide, it is important to understand the current state of GO at an international level. The International Society of Geriatric Oncology (SIOG) has several National Representatives (NRs) who act as SIOG's delegates in their respective countries. The NRs took part in this international survey exploring the state of GO practice, identifying barriers and solutions., Materials and Methods: The NRs answered open-ended questions by email from February 2020 to October 2022. The questionnaire domains included the demographic information of older adults for their countries, and the NRs' opinions on whether GO is developing, what the barriers are to developing GO, and proposed actions to remove these barriers. The demographic data of each country reported in the survey was adjusted using literature and database searches., Results: Twenty-one of thirty countries with NRs (70%) participated in this questionnaire study: 12 European, four Asian, two North American, two South American, and one Oceanian. The proportion of the population aged ≥75 years varied from 2.2% to 15.8%, and the average life expectancy also varied from 70 years to 86 years. All NRs reported that GO was developing in their country; four NRs (18%) reported that GO was well developed. Although all NRs agreed that geriatric assessment was useful, only three reported that it was used day-to-day in their countries' clinical practice (14%). The major barriers identified were the lack of (i) evidence to support GO use, (ii) awareness and interest in GO, and (iii) resources (time, manpower, and funding). The major proposed actions were to (i) provide new evidence through clinical trials specific for GO patients, (ii) stimulate awareness through networking, and (iii) deliver educational materials and information to healthcare providers and medical students., Discussion: This current survey has identified the barriers to GO and proposed actions that could remove them. Broader awareness seems to be essential to implementing GO. Additional actions are needed to develop GO within countries and can be supported through international partnerships., Competing Interests: Declaration of Competing Interest All the contributing authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Dietary practices are one of the most common modifiable risk factors for cancers. Foods rich in dietary fibers are considered protective, meanwhile fast & junk foods are risk for common cancers. Adolescence period is marked by habit formation and is thus suited for delivering behavioral intervention. Schools offer an optimal setting for planning and executing these interventions to a large number of adolescents., Objective: To assess the effectiveness of a teacher-delivered cancer-prevention education in changing dietary behaviors of school going adolescents., Methods: A cluster randomized trial was conducted in government secondary and senior secondary schools with schools as clusters. A minimum required sample of 1032 students was estimated from 16 schools with 1:1 allocation in intervention and non-intervention groups. Dietary behaviors were recorded as dichotomous variable. The determinants were recorded as per theory of planned behavior framework using Likert-scale. Two teachers from each intervention school were trained to deliver cancer prevention education with focus on role of dietary behavior. Pre-post training assessment of teachers' knowledge towards common cancers was done using a self-administered questionnaire. Gender adjusted difference-in-difference analysis was done to assess intervention effect on both healthy and unhealthy behaviors., Results: In selected schools all students from classes 8 to 10 were approached and a total of 1224 students were enrolled, of whom 1096 completed the study. The study recorded significant improvement in scores of students from intervention group compared to non-intervention group for their attitude, subjective norms, perceived behavioral control and intention towards consuming healthy and avoiding unhealthy foods. The intervention was effective in significantly improving the proportion of students limiting fried/fast/packed food & sugar sweetened beverages (OR:1.51, 95%CI:1.08,2.12,p:0.017), and consuming fruits & vegetables daily (OR:1.55, 95%CI:1.08,2.22, p:0.017) while adjusting effect of gender., Conclusion: Classroom-based cancer prevention education delivered through teachers during regular working hours is effective in improving dietary behaviors and its determinants among adolescent students. Thus, we recommend integrating a section focusing on the role of diet in cancer prevention and other lifestyle diseases in the existing school curriculum., Trial Registration: The trial was registered under Clinical Trial Registry-India with registration number CTRI/2018/12/016586, dated-10/12/2018., (© 2024. The Author(s).)

Introduction: Tobacco is a well-established risk factor for cancer, but its association with other morbidities needs consideration. The low-income and middle-income countries (LMICs) with unprecedented demographic transformation lack evidence on tobacco use and its impact on cognitive health., Aims and Methods: Using a propensity score matching approach, we utilized data from the Longitudinal Ageing Study of India. Study employed 1:1 nearest neighbor matching with the replacement methodology. We estimated the odds of the poor cognitive score and tobacco use among older adults based on five different models for ever tobacco user, former tobacco user, current tobacco user, current smokers, and current smokeless tobacco users with reference to never tobacco users., Results: The estimated average treatment effect for the treated and the untreated group has shown a higher likelihood of cognitive decline among ever (OR -0.26; 95%CI -0.43 to -0.09), current (OR -0.28; 95%CI -0.45 to -0.10), and former (OR -0.53; 95%CI -0.87 to -0.19) tobacco users compared to never tobacco users. The finding further suggests the odds of lower cognitive scores among older adults who were smokers (OR -0.53; 95%CI -0.87 to -0.19) and smokeless tobacco users (OR -0.22; 95%CI -0.43 to -0.01) as compared to never tobacco users., Conclusions: Interventions designed to prevent the incidence of cognitive impairment should focus on limiting the use of tobacco. Strategies under the tobacco-free generation initiative should be amplified in order to prevent future generations from productivity loss, premature ageing and to promote healthy aging., Implications: Evidence of a definitive association between tobacco consumption and cognition among older adults is sporadic in LMICs. Though tobacco is a risk factor for various diseases including cancer, the extent of its impact on cognitive health among the older population is limited. This study contributes to the existing literature by highlighting poor cognitive outcomes among older adults who smoke tobacco and/or consume smokeless tobacco as compared to never-tobacco users. Our findings emphasize the need to accelerate programmes related to tobacco-free generation in LMICs to reach a higher quality of life and healthy aging in pursuit of achieving the sustainable development goal of "good health and well-being.", (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Serial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle-income country (LMIC) setting., Methods: Baseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden., Results: Of 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001)., Conclusion: Paper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Purpose: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL)., Methods: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30., Results: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life., Conclusions: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To translate the Pediatric Nausea Assessment Tool (PeNAT) into Hindi and validate it in Indian pediatric cancer patients and survivors., Methods: The PeNAT-Hindi was finalized by forward and backward translations, and pilot testing. The PeNAT-Hindi was administered to 200 Hindi-speaking pediatric (4-18 y) cancer patients/survivors, in three groups. These included pediatric cancer patients who had recently received chemotherapy (n = 150); who received no chemotherapy within 5 d (n = 25) and survivors (n = 25). Construct validity was tested by comparing scores among the three groups. Test-retest reliability and criterion validity were estimated by the correlation of the first PeNAT score with the second (taken 1 h later) PeNAT score and the number of vomiting/retching episodes, respectively. Convergent validity and discriminant validity were estimated by correlating PeNAT scores with parent-assessed nausea severity, and pain, respectively. The responsiveness was tested by comparing second PeNAT scores with subsequent divergent PeNAT scores among patients reporting subjective change (improvement and worsening, respectively) in nausea severity., Results: Test-retest reliability of PeNAT-Hindi was good (intraclass correlation = 0.791). The initial PeNAT score had moderate correlation with the number of vomiting/retching episodes (Spearman ρ = 0.401). Median PeNAT scores in group 1 versus groups 2 and 3 were significantly different (p < 0.001). Initial PeNAT scores showed a moderate correlation with parent-assessed nausea (Spearman ρ = 0.657) and a weak correlation with parent-assessed pain (Spearman ρ = 0.319). The responsiveness (standardized response mean) of PeNAT-Hindi to the change in nausea severity was -1.79 (improvement) and 2.19 (worsening), respectively., Conclusion: PeNAT-Hindi showed good reliability and acceptable validity. It may be used among Hindi-speaking children for measuring nausea. The responsiveness of PeNAT-Hindi needs further evaluation., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Recent estimates suggest that the lower middle income countries in Asia carry the heaviest burden of cancer among adolescents and young adults (AYAs) (defined as age 15-39 years). A larger proportion of the population in Asia is aged 15-39 compared with the developed countries. This age group is different from the pediatric or the adult group in terms of physical, social, psychological, and financial needs. Cancer incidence, disability, survivorship needs, financial toxicity, psychosocial issues, and so on are underestimated in this group, and available literature is scarce. Global data show an increasing trend of adult-onset cancers such as colorectal, breast, pancreas, and lung in the AYA population. Data suggest that the disease biology and prognosis are different in this group; however, further research is needed. An ESMO/SIOPE/SIOP Asia survey on the care of AYA cancer patients in Asia found a suboptimal availability of AYA specialized centers in the region and identified several unmet needs including lack of training, clinical trials, and high rates of treatment abandonment. There is an urgent need for cancer care systems in Asia to develop specialized services to be able to cater to this growing burden. Training and research in this area also need to be upscaled with the goal of establishing a sustainable infrastructure and quality services to ensure that this vulnerable group receives appropriate care. Management guidelines and national health policies should consider giving special attention to this group as the World Health Assembly reinforces the inclusion of children and adolescents in cancer control programs.

Glycolysis is the fundamental cellular process that permits cancer cells to convert energy and grow anaerobically. Recent developments in molecular biology have made it evident that mitochondrial respiration is critical to tumor growth and treatment response. As the principal organelle of cellular energy conversion, mitochondria can rapidly alter cellular metabolic processes, thereby fueling malignancies and contributing to treatment resistance. This review emphasizes the significance of mitochondrial biogenesis, turnover, DNA copy number, and mutations in bioenergetic system regulation. Tumorigenesis requires an intricate cascade of metabolic pathways that includes rewiring of the tricarboxylic acid (TCA) cycle, electron transport chain and oxidative phosphorylation, supply of intermediate metabolites of the TCA cycle through amino acids, and the interaction between mitochondria and lipid metabolism. Cancer recurrence or resistance to therapy often results from the cooperation of several cellular defense mechanisms, most of which are connected to mitochondria. Many clinical trials are underway to assess the effectiveness of inhibiting mitochondrial respiration as a potential cancer therapeutic. We aim to summarize innovative strategies and therapeutic targets by conducting a comprehensive review of recent studies on the relationship between mitochondrial metabolism, tumor development and therapeutic resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The process of ferroptosis, a recently identified form of regulated cell death (RCD) is associated with the overloading of iron species and lipid-derived ROS accumulation. Ferroptosis is induced by various mechanisms such as inhibiting system Xc, glutathione depletion, targeting excess iron, and directly inhibiting GPX4 enzyme. Also, ferroptosis inhibition is achieved by blocking excessive lipid peroxidation by targeting different pathways. These mechanisms are often related to the pathophysiology and pathogenesis of diseases like cancer and Alzheimer's. Fundamentally distinct from other forms of cell death, such as necrosis and apoptosis, ferroptosis differs in terms of biochemistry, functions, and morphology. The mechanism by which ferroptosis acts as a regulatory factor in many diseases remains elusive. Studying the activation and inhibition of ferroptosis as a means to mitigate the progression of various diseases is a highly intriguing and actively researched topic. It has emerged as a focal point in etiological research and treatment strategies. This review systematically summarizes the different mechanisms involved in the inhibition and induction of ferroptosis. We have extensively explored different agents that can induce or inhibit ferroptosis. This review offers current perspectives on recent developments in ferroptosis research, highlighting the disease's etiology and presenting references to enhance its understanding. It also explores new targets for the treatment of cancer and Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The World Health Organization (WHO) has revised the classification of hematolymphoid tumors (WHO-HAEM5) in August 2022 to incorporate certain recent changes in understanding of disease biology. This article highlights the important changes, with particular reference to those most relevant to children.

Interferons (IFNs) are a class of cytokines with potent antiviral and immunomodulatory properties that regulate the immune system through multiple signaling pathways. In cancer, IFNs are vital to both tumor-intrinsic and extrinsic mechanisms that affect the quality of antitumor immunity as well as response to cancer treatments, including immunotherapy. However, there is a need for a deeper and better understanding of the mechanisms by which IFNs elicit immune signalling in cancerous cells. In this review, we focus on the IFN- dependent and independent axes in cancer as targetable hubs for new immunotherapeutic approaches to boost the treatment efficacy and to circumvent cancer resistance leading to improved clinical outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cancer is growing concern for every country. Reliable data is a source to define the magnitude of the problem, which then helps to plan for necessary action. This epidemiological study involves the collection and analysis of hospital registry data to assess the quantum of the problem of cancer over a five-year period from 2012-16 and to plan priority action., Materials and Methods: Hospital-based data for five years from 2012-2016 was retrieved from the department of radiotherapy at M. P. Shah Government Medical College, Jamnagar, Gujarat, India, and analysed to define the magnitude of the problem. All data was studied using Microsoft Excel 2016., Results: A total of 7355 patients were registered between 2012 and 2016, out of which 62 percent were male. Cancers of the cervix and uterus were discernibly less common in the Saurashtra region and accounted for only 12.37% of all cancers in females. Lung cancer was the leading cancer as a single site in males (24.13% of all cancers in males) and breast cancer in females (37.36% of all cancers in females). Head and neck cancer, all sites clubbed, was most common in males (42%). Jamnagar taluka represented around 50% of all cases at the study center., Conclusion: Tobacco-related cancers were most common in the male population, and stringent implementation of a national tobacco control program is the most appropriate measure to curtail incidences and hence mortality in this male population. Non-modifiable risk factors like gender-related cancer were more common in the female population, and resource-appropriate screening is a suitable option for these diseases. A population-based cancer registry is required to further define the pattern pertinently, or an epidemiological study is required to find causes of the noticeably lower incidence of cancer of the cervix,., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

In low-risk febrile neutropenia (LR-FN), the safety of early discontinuation of empiric antibiotics without marrow recovery is not well established. This study aimed to evaluate the safety of procalcitonin (PCT) guided early discontinuation of antibiotics in LR-FN. In this trial, children with LR-FN with an afebrile period of at least 24 h, sterile blood culture, and negative/normalized PCT were randomized at 72 h of starting antibiotics into two groups: intervention arm and standard arm. The antibiotics were stopped in the intervention arm regardless of absolute neutrophil count (ANC), while in the standard arm, antibiotics were continued for at least 7 days or until recovery of ANC (>500/mm 3 ). The primary objective was to determine the treatment failure rates, and the secondary objective was to compare the duration of antibiotics and all-cause mortality between the two arms. A total of 46 children with LR-FN were randomized to either the intervention arm ( n  = 23) or the standard arm ( n  = 23). Treatment failure was observed in 2/23 (8.7%) of patients in the intervention arm compared to 1/23 (4.3%) in the standard arm [RR: 2 (95% CI: 0.19-20.6); p  = 0.55]. The median duration of antibiotics in the intervention arm and standard arm were 3 days vs 7 days ( P = <0.001). There was no mortality in this study. PCT-guided early discontinuation of empirical antibiotics in LR-FN is feasible. There was no significant difference observed in treatment failure between the early discontinuation of antibiotics vs standard therapy. The total duration of antibiotic exposure was significantly lesser in the discontinuation arm. Further, larger multicenter studies are needed to confirm the finding of this study.

Nitrous oxide (N 2 O) is a unique anesthetic agent that has both advantages and disadvantages, especially in neurosurgical patients. Various studies evaluating the use of N 2 O in different surgical populations have been inconclusive so far. In this prospective, single-blinded, randomized study, 50 patients of either sex, aged 18-60 years, were enrolled and randomly allocated into N 2 O or N 2 O free group. Data including demographics, intraoperative vitals, blood gases, intravenous fluids, anesthetic drug consumption, brain condition, emergence and recovery time, duration of surgery and anesthesia, duration of postoperative ventilation, perioperative complications, condition at discharge, and duration of intensive care unit & hospital stay were recorded. There was no significant difference in intensive care unit or hospital stay between the groups. However, a significant difference in intraoperative heart rate and mean arterial pressure was observed. The incidence of intraoperative tachycardia and hypotension was significantly higher in the N 2 O free group. Other intra- and post-operative parameters, perioperative complications, and conditions at discharge were comparable. Use of N 2 O anesthesia for cerebellopontine tumor surgery in good physical grade and well-optimized patients neither increases the length of intensive care unit or hospital stay nor does it affect the complications and conditions at discharge. However, future studies in poor-grade patients with large tumors and raised intracranial pressure will be required to draw a definitive conclusion.

Historically, KRAS has been considered 'undruggable' inspite of being one of the most frequently altered oncogenic proteins in solid tumors, primarily due to the paucity of pharmacologically 'druggable' pockets within the mutant isoforms. However, pioneering developments in drug design capable of targeting the mutant KRAS isoforms especially KRAS G12C -mutant cancers, have opened the doors for emergence of combination therapies comprising of a plethora of inhibitors targeting different signaling pathways. SHP2 signaling pathway, primarily known for activation of intracellular signaling pathways such as KRAS has come up as a potential target for such combination therapies as it emerged to be the signaling protein connecting KRAS and the immune signaling pathways and providing the link for understanding the overlapping regions of RAS/ERK/MAPK signaling cascade. Thus, SHP2 inhibitors having potent tumoricidal activity as well as role in immunomodulation have generated keen interest in researchers to explore its potential as combination therapy in KRAS mutant solid tumors. However, the excitement with these combination therapies need to overcome challenges thrown up by drug resistance and enhanced toxicity. In this review, we will discuss KRAS and SHP2 signaling pathways and their roles in immunomodulation and regulation of tumor microenvironment and also analyze the positive effects and drawbacks of the different combination therapies targeted at these signaling pathways along with their present and future potential to treat solid tumors., (Copyright © 2024. Published by Elsevier Inc.)

RNA therapeutics have emerged as potential treatments for genetic disorders, infectious diseases, and cancer. RNA delivery to target cells for efficient therapeutic applications remains challenging due to instability and poor uptake. Polymeric nanoparticulate delivery systems offer stability, protection, and controlled release. These systems shield RNA from degradation, enabling efficient uptake and extended circulation. Various polymeric nanoparticle platforms have been explored, including lipid-based nanoparticles, polymeric micelles, dendrimers, and polymer-drug conjugates. This review outlines recent breakthroughs of recent advances, design principles, characterization techniques, and performance evaluation of these delivery systems. It highlights their potential in translating preclinical studies into clinical applications. Additionally, the review discusses the application of polymeric nanoparticles in ophthalmic drug delivery, particularly for medications that dissolve poorly in water, and the progress made in siRNA-based therapies for viral infections, autoimmune diseases, and cancers. SiRNA holds great promise for precision medicine and therapeutic intervention, with the ability to target specific genes and modulate disease-associated pathways. The versatility and potency of siRNA-based drugs offer a broader scope for therapeutic intervention compared to traditional biological drugs. As research in RNA therapeutics continues to advance, these technologies hold tremendous potential to revolutionize the treatment of various diseases and improve patient outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although cancers emerge rapidly and cancer cells divide aggressively, which affects our vital organ systems. Recently, cancer treatments are targeted immune systems mediating intrinsic cellular mechanisms. Natural efficacious polyphenols have been exhibited to help prevent most cancers and reverse the progression of cancers., Methods: Many resources have been used to know the promising role of polyphenols in preventing and treating cancers. The electronic databases include Science Direct, Google, Google Scholar, PubMed, and Scopus. The search was limited to the English language only., Results: Polyphenols have been reported as anti-metastatic agents that explore the promising role of these compounds in cancer prevention. Such agents act through many signaling pathways, including PI3K/Akt and TNF-induced signaling pathways. The chemical modifications of polyphenols and the structure-activity relationships (SARs) between polyphenols and anticancer activities have also been discussed., Conclusion: Many research papers were reported to explain the anti-cancer potential of Polyphenols, The SARs between polyphenols and anti-cancer activities, which correlate structures of polyphenols with significant chemotherapeutic action. The mechanism of anti-cancer potential is to be added for searching for new anti-cancer natural products., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The aim of the study was to perform the first meta-analysis for assessment of the pooled risk of malignancy of each category of the Sydney system for reporting of lymph nodal aspirates along with the evaluation of diagnostic accuracy., Methods: PubMed/MEDLINE and Embase were searched with the following keywords: "(Lymph node) AND (fine needle aspiration biopsy) OR (International system OR Sydney system)" in the timeframe 2020 to August 4, 2023. The selected articles were assessed for the risk of bias by the QUADAS-2 tool. The meta-analysis for sensitivity (SN) and specificity for each cut-off, that is, "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive" for the lesions, was carried out after excluding the inadequate samples in each study. To assess the diagnostic accuracy, summary receiver operating characteristic curves were constructed, and the diagnostic odds ratio was pooled in both scenarios., Results: Nine studies, all of which were retrospective cross-sectional studies, were evaluated with a total of 13,205 cases. The SN and specificity for the "atypical and higher risk categories" considered positive for malignancy were 97% (95% CI, 95-99%) and 96% (95% CI, 91-98%), respectively. The SN and specificity for the "suspicious of malignancy and higher risk categories" considered positive for malignancy were 91% (95% CI, 85-95%) and 99% (95% CI, 97-100%), respectively. The SN and specificity for the "malignant" considered positive for malignancy were 75% (95% CI, 65-84%) and 100% (95% CI, 99-100%), respectively. The pooled area under the curve was 99-100% for each of the cut-offs., Conclusion: This meta-analysis highlights the accuracy of the Sydney system in reporting lymph node aspirates. It exhibits the significance of the "suspicious" and "malignant" categories in diagnosing malignancy and of the "benign" category in excluding malignancy., (© 2023 S. Karger AG, Basel.)

Hypoxia is a pathophysiological condition characterized by oxygen deficiency in tissues, which negatively affects normal biological functions. It is a typical microenvironment character of almost all solid tumours. Noncoding RNA are small functional RNA molecules that regulate gene expression at chromatin and posttranscriptional levels. Micro-RNAs (miRNAs) are a type of noncoding RNA and are ~12-22 nucleotides long that are crucial in regulating gene expression by partnering with the mRNAs of protein-coding genes. It is widely reported that miRs play an important role in various key processes and pathways during tumour formation, as well as advancement in hypoxic tumors by influencing the HIF pathway. The role of miRNAs in hypoxic tumours, namely in pancreatic, kidney, breast, lung and colorectal, are described. These miRNAs have immense potential as diagnostic and prognostic biomarkers for early cancer detection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A needs to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Anuranjana PV et al.)

Background: Recapitulating the tumor microenvironment (TME) in vitro remains a major hurdle in cancer research. In recent years, there have been significant strides in this area, particularly with the emergence of 3D spheroids as a model system for drug screening and therapeutics development for solid tumors. However, incorporating macrophages into these spheroid cultures poses specific challenges due to the intricate interactions between macrophages and cancer cells., Methods: To address this issue, in this study, we established a reproducible healthy multicellular 3D spheroid culture with macrophage infiltrates in order to mimic the TME and modulate the drug's efficacy on cancer cells in the presence of macrophages. A 3D spheroid was established using the human cancer cell line CAL33 and THP1 cell derived M0 macrophages were used as a source of macrophages. Cellular parameters including tumour metabolism, health, and mitochondrial mass were analysed in order to establish ideal conditions. To modulate the interaction of cancer cells with macrophage the ROS, NO, and H 2 O 2 levels, in addition to M1 and M2 macrophage phenotypic markers, were analyzed. To understand the crosstalk between cancer cells and macrophages for ECM degradation, HSP70, HIF1α and cysteine proteases were examined in spheroids using western blotting and qPCR., Results: The spheroids with macrophage infiltrates exhibited key features of solid tumors, including cellular heterogeneity, metabolic changes, nutrient gradients, ROS emission, and the interplay between HIF1α and HSP70 for upregulation of ECM degradading enzymes. Our results demonstrate that tumor cells exhibit a metabolic shift in the presence of macrophages. Additionally, we have observed a shift in the polarity of M0 macrophages towards tumor-associated macrophages (TAMs) in response to cancer cells in spheroids. Results also demonstrate the involvement of macrophages in regulating HIF-1α, HSP70, and ECM degradation cysteine proteases enzymes., Conclusions: This study has significant implications for cancer therapy as it sheds light on the intricate interaction between tumor cells and their surrounding macrophages. Additionally, our 3D spheroid model can aid in drug screening and enhance the predictive accuracy of preclinical studies. The strength of our study lies in the comprehensive characterization of the multicellular 3D spheroid model, which closely mimics the TME., (© 2023. The Author(s).)

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location., Competing Interests: Declaration of interests CA holds a patent for a laparoscopic instrument with the University of Nebraska, and serves in leadership positions and committees in the Society of Surgical Oncology, American College of Surgeons, Indian Association of Surgical Oncology, The Global Forum of Cancer Surgeons, Basavatarakam Indo-American Cancer Hospital and Research Institute, National Cancer Institute, National Comprehensive Cancer Network, and Accreditation Council for Graduate Medical Education. SC's current affiliation is Janssen (Boston, MA, USA) where he began work in June, 2022. MT received grants and contracts from Chugai, Takeda, Pfizer, Taiho, Japan Breast Cancer Research Group, Kyoto Breast Cancer Research Network, Eisai, Eli Lilly and Company, Daiichi Sankyo, AstraZeneca, Astellas, Shimadzu, Yakult, Nippon Kayaku, AFI Technology, Luxonus, Shionogi, GL Sciences, and Sanwa Shurui; payments or honoraria from Chugai, Takeda, Pfizer, Kyowa–Kirin, Taiho, Eisai, Daiichi Sankyo, AstraZeneca, Eli Lilly and Company, MSD, Exact Science, Novartis, Shimadzu, Yakult, Nippon Kayaku, Devicore Medical Japan, and Sysmex; participates in the data safety monitoring board or advisory board of Daiichi Sankyo, Eli Lilly and Company, BMS, Athenex Oncology, Bertis, Terumo, and Kansai Medical Net; and serves as an Associate Editor for British Journal of Cancer, Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Oncology, Asian Journal of Surgery, and Asian Journal of Breast Surgery. LN received honoraria for speaking and educational events from Duke University, University of Chicago, Dana-Farber Cancer Institute, Mayo Clinic Jacksonville, BioAscend, MJH Healthcare Holdings, Society of Surgical Oncology, and American Cancer Society; serves on the Johns Hopkins Data Safety Monitoring Board for KALPAS Study and Duke University Cancer Center SPORE External Advisory Board; holds leadership roles in the Board of Directors, American Association for Cancer Research (unpaid/non-salaried), Board of Directors, SHARE Cancer Patient Support Organization (unpaid/non-salaried), and the Susan G Komen Scientific Advisory Board (unpaid/non-salaried). HM-S received payment or honoraria from Merck and Bristol Myers Squibb. AFR served as a co-lead of the implementation group of WHO's Global Breast Cancer Initiative, and has stock units as an employee of Hologic. ITR received honoraria from AstraZeneca and MSD. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The ubiquitin proteasomal system (UPS) represents a highly regulated protein degradation pathway essential for maintaining cellular homeostasis. This system plays a critical role in several cellular processes, which include DNA damage repair, cell cycle checkpoint control, and immune response regulation. Recently, the UPS has emerged as a promising target for cancer therapeutics due to its involvement in oncogenesis and tumor progression. Here we aim to summarize the key aspects of the UPS and its significance in cancer therapeutics. We begin by elucidating the fundamental components of the UPS, highlighting the role of ubiquitin, E1-E3 ligases, and the proteasome in protein degradation. Furthermore, we discuss the intricate process of ubiquitination and proteasomal degradation, emphasizing the specificity and selectivity achieved through various signaling pathways. The dysregulation of the UPS has been implicated in cancer development and progression. Aberrant ubiquitin-mediated degradation of key regulatory proteins, such as tumor suppressors and oncoproteins, can lead to uncontrolled cell proliferation, evasion of apoptosis, and metastasis. We outline the pivotal role of the UPS in modulating crucial oncogenic pathways, including the regulation of cyclins, transcription factors, Replication stress components and DNA damage response. The increasing recognition of the UPS as a target for cancer therapeutics has spurred the development of small molecules, peptides, and proteasome inhibitors with the potential to restore cellular balance and disrupt tumor growth. We provide an overview of current therapeutic strategies aimed at exploiting the UPS, including the use of proteasome inhibitors, deubiquitinating enzyme inhibitors, and novel E3 ligase modulators. We further discuss novel emerging strategies for the development of next-generation drugs that target proteasome inhibitors. Exploiting the UPS for cancer therapeutics offers promising avenues for developing innovative and effective treatment strategies, providing hope for improved patient outcomes in the fight against cancer., Competing Interests: Declaration of competing interest The Authors declare no conflicts of interest in connection with this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)