GALNT14 in association with GDF-15 promotes stemness and drug resistance through ß-catenin signalling pathway in breast cancer.

BACKGROUND: Altered glycosylation plays a role in carcinogenesis. GALNT14 promotes cancer stem-like properties and drug resistance. GDF-15 is known to induces drug resistance and stemness markers for maintenance of breast cancer (BC) stem-like cell state. Currently there is lack of data on association of GDF-15 and GALNTs. In this study, the expression and interaction of GALNT14 and GDF-15 with stemness (OCT4 and SOX2) and drug resistance (ABCC5) markers were evaluated in BC. METHODS: We investigated tumour tissue from 30 BC patients and adjacent non-tumour tissues. Expression of serum GALNT14 from BC patients and matched healthy controls was evaluated. Expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin in BC tissue was determined by RT-PCR. Knockdown of GALNT14 and GDF-15 in the MCF-7 cell line was done through siRNA, gene expression and protein expression of ß-catenin by western blot were determined. RESULTS: A significant increase in the expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin was observed in BC tumour tissues compared to adjacent non-tumour tissues. The serum level of GALNT14 was significantly high in BC patients (80.7 ± 65.3 pg/ml) compared to healthy controls (12.2 ± 9.12 pg/ml) (p < 0.000). To further analyse the signalling pathway involved in BC stemness and drug resistance, GALNT14 and GDF-15 were knocked down in the MCF-7 cell line, and it was observed that after knockdown, the expression level of OCT4, SOX2, ABCC5, and ß-catenin was decreased, and co-knockdown with GALNT14 and GDF-15 further decreased the expression of genes. CONCLUSION: It can be concluded that GALNT14, in association with GDF-15, promotes stemness and intrinsic drug resistance in BC, possibly through the ß-catenin signalling pathway.

Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.

Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m2), Cyclophosphamide (600 mg/m2) with or without Taxane (75-175 mg/m2) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

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.

Cost analysis of telemedicine use in paediatric nephrology-the LMIC perspective.

BACKGROUND: The overall cost of managing chronic diseases is a significant barrier to accessing complete and timely healthcare, especially in rural and geographically isolated areas. This cost disparity becomes more pronounced in the case of children and more so in under-resourced regions of the world. In the era of COVID-19, as the need for physical distancing increased, there was a transition in approach to healthcare provision to telemedicine consultations. This study evaluates the cost saving using teleconsultations in a paediatric nephrology clinic. METHODS: This prospective cohort study was conducted at AIIMS Jodhpur, a tertiary care centre in western Rajasthan from March 2021 to October 2022. All consecutive paediatric (29 days-18 years) patients attending telemedicine services for kidney-related illness were enrolled. Basic demographic details were collected. Cost analysis was done after 6 months, regarding perceived cost savings for the patient and family by using telehealth for follow-up during 6 months starting from enrolment. RESULTS: A total of 112 patients were enrolled; 266 teleconsultations attended; 109 patients who could be followed up saved INR 457,900 during 6 months of follow-up. The average cost saving was INR - 1577/patient/visit. Patients saved 4.99% of the family income (median 2.16% (IQR 0.66-5.5)). The highest expenditure per visit was incurred for food and transport. The median distance from the residence to the clinic was 122.5 km (IQR 30-250). Over the 6-month study period, patients saved a travel distance of 83,274 km (743 km/patient). CONCLUSIONS: The use of telemedicine as a follow-up method helps save significant costs and distances travelled by patients. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Upfront debulking surgery or delayed surgery after neoadjuvant chemotherapy for advanced-stage epithelial ovarian cancer: Comparison of survival from a noncancer center in India.

BACKGROUND: In advanced-stage epithelial ovarian cancer (EOC) standard of care is upfront debulking surgery (UDS) followed by adjuvant chemotherapy. Interval debulking surgery after neoadjuvant chemotherapy(NACT-IDS) is a reasonable alternative. METHODS: This study was a retrospective review of patients of Stage III/IV EOC treated either by UDS or NACT-IDS between January 2016 and December 2018 to report the comparison of progression-free survival(PFS) and overall survival(OS) of patients with advanced-stage EOC treated with either UDS or NACT-IDS. RESULTS: Out of 50 patients, 19 (38%) underwent UDS, and 31 (62%) received NACT. The mean follow-up duration was 27.7 months. No gross residual disease was achieved in 52.6% of the UDS group and in 70.4% of the NACT-IDS group. The median PFS of 20 and 30 months was observed in the UDS and NACT-IDS groups, respectively (log-rank P = 0.054). The median OS was 36 months in the NACT-IDS group and could not be reached in the UDS group (log-rank P = 0.329). Only residual disease was significantly associated with survival (hazards ratio 3.03, 95% confidence interval: 1.19-7.74) on multivariate Cox regression analysis. CONCLUSIONS: In advanced-stage EOC, the survival outcomes of NACT-IDS are comparable with those of UDS. Apart from the patient-specific parameters, the decision for UDS or NACT-IDS should take in account the expertise of the surgeon and the institutional capacity as a whole.

Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancer: Findings from a tertiary care institute in western part of India.

BACKGROUND: Immune checkpoint inhibitors targeting either programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have been established as a novel target for immunotherapy in non-small cell lung cancer (NSCLC). Prevalence of PD-L1 expression in NSCLC varies from 13% to 70%, with sparse data from the Indian subcontinent. In this study, we looked at PD-L1 expression and its association with demographic, clinical, radiologic and pathologic parameters in NSCLC patients. METHODS: This was an observational study carried over a period of 18 months in which 65 patients of NSCLC were included. Immunohistochemistry (IHC) for PD-L1 was done using an automated IHC stainer and testing was performed using PD-L1 IHC CAL10. For statistical analysis, unpaired t test, Chi square test, Fisher's exact test and binomial logistic regression were used. P < 0.05 was taken to be statistically significant. RESULTS: Mean age of the patients was 62.9 ± 9.2 years, and majority (87.3%) of them were males. Seventeen (26.2%) patients expressed PD-L1, among whom 10 had high PD-L1 expression (≥50%) and 7 had low PD-L1 expression (1-49%). PD-L1 expression was seen in 13 out of 43 cases of squamous cell carcinoma (SCC) and 4 out of 15 cases of adenocarcinoma. On applying binomial logistic regression analysis, association between smoking and PD-L1 expression was found to be insignificant. CONCLUSION: Almost a quarter of NSCLC cases were PD-L1 positive without any difference in expression between SCC and adenocarcinoma. PD-L1 status was not associated with any specific demographic, clinical or radiologic parameter including the histologic subtype.

Different glassy characteristics are related to either caging or dynamical heterogeneity.

Despite the enormous theoretical and application interests, a fundamental understanding of the glassy dynamics remains elusive. The static properties of glassy and ordinary liquids are similar, but their dynamics are dramatically different. What leads to this difference is the central puzzle of the field. Even the primary defining glassy characteristics, their implications, and if they are related to a single mechanism remain unclear. This lack of clarity is a severe hindrance to theoretical progress. Here, we combine analytical arguments and simulations of various systems in different dimensions and address these questions. Our results suggest that the myriad of glassy features are manifestations of two distinct mechanisms. Particle caging controls the mean, and coexisting slow- and fast-moving regions govern the distribution of particle displacements. All the other glassy characteristics are manifestations of these two mechanisms; thus, the Fickian yet non-Gaussian nature of glassy liquids is not surprising. We discover a crossover, from stretched exponential to a power law, in the behavior of the overlap function. This crossover is prominent in simulation data and forms the basis of our analyses. Our results have crucial implications on how the glassy dynamics data are analyzed, challenge some recent suggestions on the mechanisms governing glassy dynamics, and impose strict constraints that a correct theory of glasses must have.

An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Comparison of sequential versus simultaneous integrated boost of volumetric modulated arc therapy in treatment of oropharyngeal carcinoma.

OBJECTIVE: Volumetric modulated arc therapy (VMAT) is a useful treatment technique that can reduce treatment time while producing improved dose distribution to target structures. The main aim of the study is to evaluate the outcome of oropharyngeal cancer patients treated with VMAT, sequential (SEQ) versus simultaneous integrated boost (SIB) technique in terms of survival and failures and to assess late radiation toxicities with their dosimetric parameters. MATERIAL AND METHODS: Total 54 patients of histologically proved oropharyngeal cancer patients treated by definitive radiotherapy using VMAT technique in January 2019 to December 2020 were followed up and evaluated in terms of survival, patterns of failure and late radiation toxicities by RTOG toxicity criteria. RESULTS: After a median follow up of 12 months, overall survival (OS) and disease free survival (DFS) were 64.8% and 48.1% respectively. In terms of patterns of failure, 44.4% showed local recurrence, 7.4% as regional relapse and 3.7% showed distant metastasis. While comparing sequential versus SIB, no significant difference was found in OS (64.9% vs. 59.8%, p = 0.689), DFS (52.8% vs. 35.3%, p = 0.266), local control (LC) (58.3% vs. 47.1%, p = 0.437) and regional control (RC) (94.3% vs. 88.2%, p = 0.151) respectively. Among late radiation toxicities, the most common were xerostomia (42.2% for SEQ and 24.2% for SIB group), dysphagia (33.3% for SEQ and 15.1% for SIB group) and hoarseness of voice (15.1% for SEQ and 12.1% for SIB group). CONCLUSION: SIB technique proved better than SEQ technique in terms of pattern of failure or late toxicity, but no significant difference can be reported.

Impact of Radiotherapy on Quality of Life in T2 and Early T3 Laryngeal Carcinoma.

Objective- To acknowledge patient-perceived voice-related and overall quality of life (QOL) in addition to disability index based on the validated voice-related quality of life survey (VRQOL), WHOQOL-BREF, and WHO DAS II questionnaires in T2 and early T3 laryngeal tumors after definitive radiotherapy. Methods- 35 patients of T2(15) and early T3(20) tumors were enrolled, assessed with three questionnaires of VRQOL, WHOQOL-BREF, and WHO DAS II before the start of radiotherapy, then at 12 and 24 weeks after radiotherapy, and the results were analyzed. Results- All 35 (100%) patients had significant vocal deterioration with a raw VRQOL score of more than 25 at the beginning, which significantly improved at 12 weeks post-radiotherapy (p < 0.5). However, VRQOL scores at the 12th and 24th weeks were statistically insignificant. On comparing the WHOQOL-BREF and WHO DAS II, domains of physical health, psychological health, and participation in society showed significant improvement in both the groups after radiotherapy except distress scores in T2 laryngeal cancers, where pre and post-radiotherapy scores were not significantly different suggesting residual distress. Conclusion- The QOL parameters improve significantly with treatment, however, there exists a persistence of residual distress even at 24 weeks after radiotherapy and hence, routine involvement of clinical psychologists should be emphasized in practice to alleviate anxiety, distress, and concerns regarding disease outcome and recurrence. 12 to 24 weeks post-radiotherapy can be an optimum time to gauge the improvement in the patient-related QOL outcome parameters and does not differ much between these durations. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03397-3.

Is Hypoglycemia Secondary to Metastatic Retroperitoneal Sarcoma - A Therapeutic Challenge? Case Report and Review of Literature.

Most soft tissue sarcomas afflict the extremities; however, the retro peritoneum can also be affected rarely. Retroperitoneal sarcomas are relatively asymptomatic. Although tumor-induced hypoglycemia is rare in tumors other than insulinomas, extrapancreatic tumors are a subset that displays this phenomenon. The occurrence of hypo-insulinemic hypoglycemia with low GH and IGF-1 should prompt consideration of the secretion of a hypoglycemic substance impeding the secretion of insulin and GH, such as IGF-2 or one of its related substances. The present case report is of a 38-year-old male with retroperitoneal round cell sarcoma with liver metastasis with severe symptomatic hypoglycemia who was managed with multipronged symptomatic therapy and oncological management after which he had shown significant improvement in hypoglycemic episodes and symptom profile. A literature review revealed our case report to be the first reported case of a young male (preponderance in the older population) with hypoglycemia associated with retroperitoneal sarcoma which presented with liver metastasis and the only one treated with Gemcitabine /Docetaxel. The presence of these features might point toward a poorer prognosis in a disease with an already dismal course. All these points towards the need for further research regarding intensified oncological treatment after evidence-based prognostication of high-risk groups and modalities for the management of symptomatic hypoglycemia such as Somatostatin analogs and glucagon which aid in symptom control.

Deregulation of miR-10b and miR-21 Correlate with Cancer Stem Cells Expansion through the Apoptotic Pathway in Prostate Cancer.

BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate important cellular processes such as tumorigenesis, cell proliferation, and apoptosis. Cancer stem cells are a subset of cells that control metastasis and cell proliferation. In this study, we focus on the roles of miR-10b, miR-21 and correlate with cancer stem cells through the apoptotic pathway in different stages of prostate cancer (PCa). METHODS: In total, 45 patients, each group with Benign prostatic hyperplasia (BPH), localised PCa, and metastatic PCa, were recruited. MicroRNA and gene expression were estimated through quantitative polymerase chain reaction. Flow cytometry was used to characterise prostate cancer stem cells (PCSCs), estimate reactive oxygen species (ROS), apoptosis and chemiluminescent immunoassay was used to estimate interleukin 6 (IL-6), tumour necrosis factor (TNF-α), prostate-specific antigen (PSA), and testosterone. RESULTS: The fold change mean expressions of miR-21, miR-10b, Cytochrome C, and B-cell lymphoma 2 (BCL-2) were significantly upregulated in localised and metastatic PCa compared with BPH. In contrast, the mean fold change expressions of Bcl-2-associated X protein (BAX), Caspase-3, Caspase-9, and Second mitochondria-derived activator of caspase (SMAC) were lower in localised and metastatic PCa compared to BPH. The levels of IL-6, TNF-α, ROS, PSA and testosterone also showed a significant increase while apoptosis was decreased in both localized PCa and metastatic PCa as compared with BPH. In bioinformatics analyses, we found a similar pattern of miRNAs and gene expression in PCa databases. Our study also found a high expression of CD44+/CD24- and CD44+/CD133+ in localised and metastatic PCa compared with BPH. CONCLUSION: Our findings suggest miR-10b and miR-21 promote PCSCs and may target apoptotic genes involved in PCa pathogenesis; these miRNAs could be used as diagnosis biomarkers of PCa. In PCa pathogenesis and PCSCs regulation, the interaction between these two players is crucial and will help develop new PCa therapeutic targets.

Multi-modality management of chondrosarcoma of scapula: A case report and review of literature.

Chondrosarcoma are malignant tumours in which neoplastic cells produce cartilage. The most commonly affected sites are pelvis, femur, humerus and ribs. Scapula involvement is relatively rare. Surgery remains the primary modality of treatment for chondrosarcoma. Radiotherapy is used as an adjuvant therapy in high grade tumours and in cases of residual disease. Present study reports a rare case of scapular chondrosarcoma in a 37 year old male, managed with multimodality treatment and discusses briefly the prognostic parameters and treatment modalities. Only few studies have discussed about scapular chondrosarcoma and more studies with larger number of patients are needed to develop an evidence-based treatment and follow-up protocol for these patients.

Correlation of hsa miR-101-5p and hsa miR-155-3p Expression With c-Fos in Patients of Oral Submucous Fibrosis (OSMF) and Oral Squamous Cell Carcinoma (OSCC).

Aim: MicroRNAs have been widely acknowledged as a diagnostic, prognostic, and/or therapeutic biomarker for the progression of OSCC, but the correlation of hsa-miR-101-5p and hsa-miR-155-3p is yet to be established with c-Fos in OSCC and OSMF. Methodology: An observational study enrolled 40 patients divided into 2 groups: Group I-21 OSMF patients without malignant transformation, Group II-19 patients with locally advanced, large-operable, or metastatic OSCC, after applying inclusion and exclusion criteria. Both miRNAs were extracted and analyzed from the tissue sample excised from the involved site. The linear regression analysis of the expression of hsa-miR-155-3p, hsa-miR-101-5p, and levels of c-fos in OSMF and OSCC patients and its correlation for habits, age, and gender were evaluated. Results: The expression of hsa-miR-101-5p was 0.81 times downregulated in OSCC tissue compared to OSMF, whereas hsa-miR-155-3p and c-fos were both upregulated 9.30 times and 1.75 times, respectively, in OSCC tissue. In Gutkha and tobacco chewers, the hsa-miR-155-3p expression could explain 12.3% (p = 0.031) for Gutkha chewers, whereas c-fos could explain 38.6% of the cases (p = 0.020) for tobacco chewers. The expression of hsa-miR-101-5p and hsa-miR-155-3p explained 43.7% and 59.5% of OSCC cases in alcoholics, respectively. Interestingly, in non-alcoholics, hsa-miR-155-3p and hsa-miR-101-5p were significant predictors of OSCC. Conclusion: Downregulation of tumor-suppressor hsa-miR-101-5p and upregulation of proto-onco hsa-miR-155-3p is responsible for intricate regulation of the progression of OSMF to OSCC via deregulated expression of c-Fos and tobacco chewing and advancing age is significant contributors for OSCC.

In silico analysis of differentially expressed-aberrantly methylated genes in breast cancer for prognostic and therapeutic targets.

Breast cancer (BC) is the leading cause of death among women across the globe. Abnormal gene expression plays a crucial role in tumour progression, carcinogenesis and metastasis of BC. The alteration of gene expression may be through aberrant gene methylation. In the present study, differentially expressed genes which may be regulated by DNA methylation and their pathways associated with BC have been identified. Expression microarray datasets GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724 and one DNA methylation profile dataset GSE20713 were downloaded from Gene Expression Omnibus database (GEO). Differentially expressed-aberrantly methylated genes were identified using online Venn diagram tool. Based on fold change expression of differentially expressed-aberrantly methylated genes were chosen through heat map. Protein-protein interaction (PPI) network of the hub genes was constructed by Search Tool for the Retrieval of Interacting Genes (STRING). Gene expression and DNA methylation level of the hub genes were validated through UALCAN. Overall survival analysis of the hub genes was analysed through Kaplan-Meier plotter database for BC. A total of 72 upregulated-hypomethylated genes and 92 downregulated-hypermethylated genes were obtained from GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724, and GSE20713 datasets by GEO2R and Venn diagram tool. PPI network of the upregulated-hypomethylated hub genes (MRGBP, MANF, ARF3, HIST1H3D, GSK3B, HJURP, GPSM2, MATN3, KDELR2, CEP55, GSPT1, COL11A1, and COL1A1) and downregulated-hypermethylated hub genes were constructed (APOD, DMD, RBPMS, NR3C2, HOXA9, AMKY2, KCTD9, and EDN1). All the differentially expressed hub genes expression was validated in UALCAN database. 4 in 13 upregulated-hypomethylated and 5 in 8 downregulated-hypermethylated hub genes to be significantly hypomethylated or hypermethylated in BC were confirmed using UALCAN database (p < 0.05). MANF, HIST1H3D, HJURP, GSK3B, GPSM2, MATN3, KDELR2, CEP55, COL1A1, APOD, RBPMS, NR3C2, HOXA9, ANKMY2, and EDN1 were significantly (p < 0.05) associated with poor overall survival (OS). The identified aberrantly methylated-differentially expressed genes and their related pathways and function in BC can serve as novel diagnostic and prognostic biomarkers and therapeutic targets.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 4 Given name: [Jeewan Ram] Last name [Vishnoi]. Also, kindly confirm the details in the metadata are correct.It is correct.

Challenges Faced by Cancer Patients in Receiving Health Services During the COVID-19 Pandemic in a Tertiary Care Hospital in Rajasthan.

BACKGROUND: Amidst the COVID-19 pandemic, cancer patients may have faced difficulty accessing health care. This study explored the challenges experienced by cancer patients in availing of healthcare during the pandemic, as well as the vaccination status and prevalence of COVID-19 infection among cancer patients in the year 2021. METHOD: A cross-sectional study was conducted in a tertiary care hospital in Jodhpur, Rajasthan, to interview 150 patients from the oncology department using convenience sampling. Face-to-face interviews lasted for 20-30 minutes. The first segment of the pretested semi-structured questionnaire was directed at obtaining the patient's socio-demographic characteristics, while the second segment focused on the problems that patients encountered during the pandemic in receiving cancer care. The data were analyzed using Statistical Packages for Social Sciences (SPSS) software (IBM Corp., Armonk, NY). RESULTS: Several constraints, such as a lack of transportation services, difficulty in availing outpatient department (OPD) and teleconsultation services, long waiting times, and deferred surgeries and therapies, have hampered cancer care. COVID-19 mitigation measures further imposed additional stress and financial burden on cancer patients. Moreover, there was low vaccination coverage among cancer patients, which increases their probability of acquiring an infection. CONCLUSION: Policy reforms must prioritize cancer care in India to maintain a continuum of care by ensuring medication, teleconsultation, uninterrupted treatment, and complete vaccination to decrease the risk of COVID-19 infection and facilitate patient compliance with the healthcare delivery system.

Study of MicroRNA (miR-221-3p, miR-133a-3p, and miR-9-5p) Expressions in Oral Submucous Fibrosis and Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the common types of cancer. Its progression follows a transition from oral potentially malignant disorders (OPMDs) such as oral submucous fibrosis (OSMF). Epigenetic modifiers, especially microRNAs (miRNAs), have an appreciable role in the regulation of various carcinogenic pathways which are being used as biomarkers. miRNAs may also be helpful in the differentiation of oral submucous fibrosis from oral squamous cell carcinoma. Three miRNAs, miR-221-3p, miR133a-3p, and miR-9-5p, were found differentially expressed in many cancers in the literature search supported by our preliminary database search-based screening. The literature and our functional enrichment analysis in an earlier study have reported these miRNAs to regulate carcinogenesis at various steps. In the present study, the expression of these miRNAs was examined in 34 histopathologically confirmed OSCC, 30 OSMF, and 29 control (healthy volunteers) human samples. There was a significant downregulation of miRNA-133a-3p in OSCC compared to OSMF and controls, whereas there was up-regulation in oral submucous fibrosis compared to controls. There was no significant difference in the expression of miR-221-3p between OSCC and OSMF, but an upregulation in OSCC compared to controls. miR-9-5p was also found upregulated in both OSCC and OSMF. Further, miR-133a-3p expression was negatively correlated with age, smoking, drinking status, and AJCC staging, whereas miR-9-5p expression was only positively associated with tobacco/ areca nut chewing. The ROC plots, logistic regression model generated, and the correlation between the expression of miR-9-5p and miR-133a-3p in blood and tissue suggests that these could be used as risk stratification biomarkers.

Global and promoter specific hypermethylation of tumor suppressor genes P16, SOCS1, and SHP1 in oral squamous cell carcinoma and oral submucous fibrosis.

ABSTRACTS: Aberrant methylation pattern leads to altered gene expression, that is, involved in the transformation of various cancers, including oral squamous cell carcinoma (OSCC). In the present study, an attempt has been made to examine the association of global and promoter-specific methylation of tumor suppressor genes in patients with OSCC and oral submucous fibrosis (OSMF). Promoter-specific methylation of tumor suppressor genes P16, SOCS1, and SHP1 had been studied earlier for their aberrant methylation patterns in other cancers; however, these studies were mainly conducted in-vitro or in animal models, and as such, only a few studies are available on human samples. In the present study evaluation of promoter-specific methylation of genes P16, SOCS1, and SHP1 in 76 patients' blood and tissue samples was done and compared with methylation of 35 healthy control samples using qPCR. Further, these samples were analyzed for global methylation patterns using ELISA. The results have shown a significant decreasing trend of promoter methylation (OSCC > OSMF > Controls); the methylation indices (MI) were significantly higher in OSCC than in the controls. The median MI of three genes for OSCC were P16MI (0.96), SHP1MI (0.79), and SOCS1 (0.80). Similarly, median MIs for OSMF were P16MI (0.18), SHP1 MI (0.19), and SOCS1 MI (0.5) against controls with MI (0) for each of the three genes. The global methylation %mC values were 1.9, 0.5, and 0.1, respectively. The values of MI and %mC were found to correlate with various risk factors such as tobacco, smoking, and alcohol consumption, which are positively involved in OSMF pathogenesis followed by oral cancer progression. Further, the methylation trend in tissue was reflected in blood samples, proving a window for methylation load to be used as a lesser invasive biomarker. The sensitivity and specificity of methylation load were also found reasonable. Therefore, the current study suggests that there may be a role of global and promoter-specific methylation load in the transition of OSMF to OSCC.

A rare case of benign metastasizing leiomyoma at vertebrae.

ABSTRACT: Benign metastasizing leiomyoma (BML) is a rare disease that usually occurs in women of reproductive age, with a history of uterine leiomyoma treated with hysterectomy. This may present as lesions in lungs, lymph nodes, bones, brain, mediastinum, and soft tissues. However, the most commonly affected site is the lung. Here is a case report of a patient who presented with BML at vertebral body with distant metastasis to lungs, brain, and bones. A 37-year-old female, with no known comorbidities, presented with pain in the upper back, urinary and bowel incontinence, and weakness in the bilateral lower limbs. Radiological, multiple metastases were present at D2 and D9 vertebral bodies, multiple nodular lesions were present in the lungs, and solitary lesion was found in the right frontal lobe of the brain. Histology proved it to be of myoepithelial origin with low Ki-67 index. The treatment in this case was based on hormone production suppression and radiotherapy, with no signs of progression at follow-up.

A dosemetric and radiobiological impact of VMAT and 3DCRT on lumbosacral plexuses, an underestimated organ at risk in cervical cancer patients.

Background: The purpose of this study was to evaluate dosimetric and radiobiological difference between volumetric modulated arc therapy (VMAT) and 3-dimensional conformal radiotherapy (3DCRT) in organ at risk (OAR) lumbosacral plexus (LSP) in cervical cancer patients. Materials and methods: 30 patients of cervical cancer who were treated using 3DCRT or VMAT along with chemotherapy followed by brachytherapy were enrolled. LSP was delineated retrospectively. Dosimetric and radiobiological difference was evaluated. Patients were followed for radiation induced lumbosacral plexopathy (RILSP). Results: Median follow-up was 12 months (3-16 months). 53.3% of patients were treated by 3DCRT and 46.7% by VMAT. The mean (±SD) LSP volume: 119.03 ± 15 cm3. The mean volume percentages (%) of the LSP: V5, V10, V20, V30, V40, V50, V55, and V60 were 100%, 99.8%, 99.2%, 94.3%, 84.03%, 59.7%, 0%, 0%, respectively. All patients received doses to the LSP in excess of 50 Gy, one patient received 55 Gy. A statistically significant difference was observed in the median value of V20, V30, V40, V50, D50, P2, P4, P7, P8, P9, and P10 across two different techniques of radiotherapy - VMAT and 3DCRT. None of the patients presented with RILSP. NTCP value was less in VMAT plans compared to 3DCRT, which is also statistically significant. Conclusion: RILSP is a rare and often refractory complication of pelvic radiotherapy. Advance radiotherapy technique with proper OAR delineation and constraint can prevent the occurrence of RILSP. VMAT has potential benefits for the probability of dose reduction in LSP. Further studies are required focusing on dose distribution in LSP-OAR and radiotherapy modality.