Cytotoxic evaluation of pure and doped iron oxide nanoparticles on cancer cells: a magnetic fluid hyperthermia perspective.

The need of the hour with respect to cancer treatment is a targeted approach with minimal or nil ramifications. Apropos, magnetic fluid hyperthermia (MFH) is emerging as a potential therapeutic strategy with anticipated reduced side effects for solid tumors. MFH causes cytotoxicity due to the heat generated owing to Hysteresis, Neel, and Brownian relaxation losses once magnetic nanoparticles (MNPs) carrying cancer cells are placed under an alternating magnetic field. With respect to MFH, iron oxide-based MNPs have been most extensively studied to date compared to other metal oxides with magnetic properties. The effectiveness of MFH relies on the composition, coating, size, physical and biocompatible properties of the MNPs. Pure iron oxide and doped iron oxide MNPs have been utilized to study their effects on cancer cell killing through MFH. This review evaluates the biocompatibility of pure and doped iron oxide MNPs and their subsequent hyperthermic effect for effectively killing cancer cells in vitro and in vivo.

Characteristics of Bilateral Adrenal Lesions: Experience from an Indian Tertiary Care Centre.

Introduction: The aetiologies in unilateral and bilateral adrenal lesions can be different with different clinical implications and management guidelines, the latter having aetiologies like hyperplasia, infections, infiltrative lesions and neoplasia. Bilateral tumours are more likely to have hereditary/syndromic associations. There is limited data on the clinical and pathological profile of bilateral adrenal lesions. Methods: This was a retrospective study where patients with bilateral adrenal lesions were selected from a total of 266 patients with adrenal lesions who presented to our institute between January 2016 and August 2022. The demographic, laboratory and imaging data were retrieved from the Hospital Information System and patient case files. Results: The study included 51 patients; the mean age at presentation was 51.15 years (range 14 to 82 years). Forty-eight patients (94.1%) were symptomatic at presentation with an average duration of symptoms being 10.68 months (range 10 days to 1 year). The most common presentation was adrenal insufficiency in 18 cases (38%), followed by fever in 17 cases (36%). The commonest aetiology, as revealed on histopathology, was histoplasmosis (n = 22, 43%), followed by pheochromocytoma (n = 11, 21.5%), metastases (n = 6, 11.7%), adrenal hyperplasia (n = 5, 9.8%), adrenocortical adenoma (n = 1, 1.9%), lymphoma (n = 3, 5.8%), neuroblastoma (n = 1, 1.9%), myelolipoma (n = 1, 1.9%) and tuberculosis (n = 1, 1.9%). Histoplasmosis and metastatic lesions were commonly seen in older people, and pheochromocytoma was associated with young age. 6/11 patients with a diagnosis of bilateral pheochromocytoma were associated with family history, genetic mutation and extra-adrenal involvement. Conclusion: The approach to bilateral adrenal lesions differs from that of unilateral lesions due to differences in aetiologies and the more significant role of genetics in some bilateral tumours. The age at presentation, presenting symptoms, lesion size and biochemical features help delineate varied underlying aetiologies.

Clinicopathological analysis of patients with dual malignancies: A retrospective study.

BACKGROUND: This study aims to report the increasing incidence of second primary malignancies to better understand the association of multiple primary cancers and the duration of their occurrence. Keeping in view the current trends in dual malignancies and to further emphasize the importance of screening and follow-up diagnosis, we reviewed the records of patients who were diagnosed with dual malignancies. MATERIAL AND METHODS: This is a retrospective observational study. We collected data from the hospital database, of patients presenting with either histologically proven synchronous or metachronous double primaries between January 1, 2017, and December 31, 2021. The time interval to differentiate between synchronous and metachronous has been taken as 6 months. RESULTS: During the period of five years, twenty-three patients presented with dual malignancy. Out of 23 cases, seven were synchronous (30.43%), and 16 were metachronous (69.56%). In the synchronous malignancy group, the most common site of first and second primary malignancy was breast [5 cases (71.4%) and 3 cases (42.8%), respectively]. In the metachronous malignancy group, the most common site of the first primary was breast (7 cases; 43.75%), followed by the head and neck (4 cases; 25%), and the most common site of the second primary was also the breast (6 cases; 37.5%), followed by the lung (5 cases; 31.25%). CONCLUSION: Second primary malignancies are not rare and can occur at any age. Regular follow-up and screening procedures by the treating oncologist can play a major role in early detection followed by appropriate treatment of second primary tumors.

MRI Evaluation of Microstructural and Perfusion Changes in Patients with Hemsensory Neurological Syndromes.

BACKGROUND: Hemisensory syndrome is characterized by a nondermatomal sensory deficit involving one half of the body. With the conventional imaging techniques, researches find low diagnostic yield in this condition; however, with the advancements in MRI imaging, there is hope to find the pathophysiological basis of hemisensory symptoms. OBJECTIVE: To evaluate microstructural and perfusion changes in brain parenchyma in patients with hemisensory syndrome on MRI with diffusion tensor imaging (DTI) and arterial spin labeling (ASL). MATERIAL AND METHODS: A total of 20 patients with hemisensory symptoms and 10 age-matched controls were enrolled and divided in two study groups - a) case vs. control and b) affected vs. nonaffected cerebral hemisphere in cases. Quantification of absolute cerebral blood flow (aCBF), fractional anisotropy (FA), and mean diffusivity (MD) was done in both groups. RESULTS: On ASL, there was significantly increased aCBF in thalamus on the contralateral-affected side. DTI revealed significantly decreased FA in the thalamus and increased FA in corona radiata of the affected side. There was a significant difference for MD of corona radiata between affected and nonaffected hemisphere. The mean value of MD in corona radiata is decreased on the affected side. CONCLUSION: Changes in advanced neuroimaging techniques like ASL and DTI along the pain processing pathway suggest an alteration in neuronal density and activity at the microstructural level. These findings may provide an insight into the etiopathogenesis of pain syndromes.

Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma.

The interaction between stromal and tumor cells in tumor microenvironment is a crucial factor in Mantle cell lymphoma (MCL) progression and therapy resistance. We have identified a long non-coding RNA, CERS6-AS1, upregulated in MCL and associated with poor overall survival. CERS6-AS1 expression was elevated in primary MCL within stromal microenvironment and in a subset of MCL cells adhered to stromal layer. These stromal-adhered MCL-subsets exhibited cancer stem cell signatures than suspension counterparts. Mechanistically, we found that downregulating CERS6-AS1 in MCL reduced Fibroblast Growth Factor Receptor-1 (FGFR1), expression attributed to loss of its interaction with RNA-binding protein nucleolin. In addition, using in-silico approach, we have discovered a direct interaction between nucleolin and 5'UTR of FGFR1, thereby regulating FGFR1 transcript stability. We discovered a positive association of CERS6-AS1 with cancer stem cell signatures, and Wnt signaling. Building on these, we explored potential therapeutic strategies where combining nucleolin-targeting agent with FGFR1 inhibition significantly contributed to reversing cancer stem cell signatures and abrogated primary MCL cell growth on stromal layer. These findings provide mechanistic insights into regulatory network involving CERS6-AS1, nucleolin, and FGFR1 axis-associated crosstalk between tumor cells and stromal cell interaction and highlights therapeutic potential of targeting a non-coding RNA in MCL.

Safety and Efficacy of Golimumab in Indian Patients with Active Spondyloarthritis of Ankylosing Spondylitis or Psoriatic Arthritis: A Multicenter, Noncomparative, Open-Label, Real-World Study.

BACKGROUND: The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitor therapy for most common rheumatological diseases, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in controlled clinical trials is well-studied. This study evaluated subcutaneous (SC) golimumab in Indian patients with active spondyloarthritis (SpA) of AS or PsA in a real-world setting. MATERIALS AND METHODS: This phase 4, multicenter, prospective, non-comparative, interventional, 24-week study was performed in patients (age ≥18 years) with active SpA of AS or PsA (NCT03733925). Golimumab 50 mg was given subcutaneously to the patients every 4 weeks. Safety was assessed. The proportion of patients with AS and PsA achieving ≥20% improvement in the Assessment of SpA International Society 20 (ASAS20) criteria and American College of Rheumatology 20 (ACR20) responses, respectively, at weeks 14 and 24 were efficacy endpoints. RESULTS: Of the 100 patients enrolled (men: 78 [78.0%]; mean age: 36.7 [12.02] years), 94 (94.0%) patients completed the study. Treatment-emergent adverse events with golimumab were observed in 29/100 (29.0%) patients, and nasopharyngitis and upper respiratory tract infection (5.0% each) were the most common (≥5%). Deaths were not reported. At week 14, 74.5% (95% confidence interval [CI]: 59.7; 86.1%) of patients with AS and 84.6% (95% CI: 69.5; 94.1%) of patients with PsA achieved ASAS20 and ACR20 responses, which were sustained at week 24 (ASAS20: 66.0% [95% CI: 50.7, 79.1%]; ACR20: 93.2% [95% CI: 81.3, 98.6%]), respectively. CONCLUSION: Golimumab (50 mg) administered subcutaneously was safe and effective in Indian patients with active SpA of AS or PsA during the 24-week study period with no new safety signals.

Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Ictal kissing: Review of literature and report of 5 cases.

Ictal kissing (IK) is a rare type of automatism observed during epileptic seizures. Despite its uncommon occurrence, understanding the underlying mechanisms, the role of emotions, and the level of consciousness during seizures with IK is essential in providing a comprehensive understanding of epilepsy. We describe five cases (.13%) of IK after performing a retrospective analysis of 3794 long-term, ictal video-EEGs from an epilepsy monitoring unit in Mumbai, India. Our patients with drug-resistant epilepsy showed IK had a wide epileptogenic zone. We discuss the current hypotheses on the mechanisms behind IK, the involvement of temporal lobe structures, and the implications of awareness during seizures. The review concludes by suggesting future directions for research to elucidate the complex phenomenon of IK further.

Dostarlimab: Review on success story and 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.

Dosimetric comparison between carotid-sparing IMRT and 3DCRT in early glottic cancer patients treated with definitive radiation therapy.

BACKGROUND: The purpose of this study was to evaluate the dosimetric benefits of carotid-sparing IMRT (intensity-modulated radiation therapy) over 3DCRT (three-dimensional conformal radiation therapy) in early glottic cancer patients. MATERIAL AND METHODS: Ten patients with histologically proven early-stage squamous cell cancer of glottis (T1N0), treated with definitive radiotherapy, were selected retrospectively for the dosimetric analysis. Patients were originally treated with 3DCRT technique. For comparison purpose, IMRT plans were generated for each patient. Dosimetric comparison was done between two techniques (IMRT and 3DCRT) in terms of PTV (planning target volume) coverage, HI (homogeneity index), CI (conformity index), and doses to right carotid artery, left carotid artery, and spinal cord. RESULTS: V95% for the PTV was higher in IMRT plans (98.26%) as compared to 3DCRT plans (95.12%) (P-value <0.001), whereas V105% for PTV was significantly higher in 3DCRT plans (16.77%) as compared to IMRT plans (0.32%) (P-value 0.11). In terms of both HI and CI, IMRT plans showed better conformity as compared to 3DCRT plans, with statistically significant difference. Both right and left carotid arteries' average mean and maximum doses were significantly lower in IMRT plans as compared to 3DCRT plans (P-value <0.001). IMRT plans resulted in significant carotid-sparing as compared to 3DCRT plans in terms of V35 and V50 (P-value <0.001). CONCLUSION: Carotid-sparing IMRT resulted in better PTV coverage and lower carotid artery dose as compared to 3DCRT in early glottic cancer patients.

Racemose neurocysticercosis: a case series.

Neurocysticercosis (NCC) is a common parasitic condition of the central nervous system in certain parts of the world. The racemose variety of NCC is distinct from the commonly seen parenchymal form. It frequently infiltrates the basal cisterns and Sylvian fissures. Imaging plays a vital role in the diagnosis; however, as their signal intensity is similar to cerebrospinal fluid and due to the absence of enhancement in most cases, imaging diagnosis is often difficult on the conventional MRI sequences. Here, we present five cases of racemose NCC to emphasize the importance of a heavily T2-weighted sequence (Fast Imaging Employing Steady-state Acquisition) sequence in the diagnosing this entity.

Comparative Analysis of VMAT and IMRT Techniques: Evaluation of Dose Constraints and Bone Marrow Sparing in Cervical Cancer Patients Undergoing Chemoradiotherapy.

BACKGROUND: Carcinoma of the cervix is a globally significant cause of morbidity and mortality among women. Concurrent chemoradiotherapy, a standard approach for locally advanced cervical cancer, invariably involves pelvic irradiation. Although this strategy is effective, it inevitably affects the pelvic bone marrow, a crucial hematopoietic site, and leads to hematological toxicity The potential of IMRT to spare bone marrow in pelvic irradiation settings has been an area of significant interest, with the aim to mitigate the hematological toxicity associated with pelvic radiotherapy. Radiotherapy techniques have evolved in terms of conformity and normal tissue sparing. Our study intends to explore the use of BM sparing techniques among patients of carcinoma cervix. PATIENTS AND METHODS: Twenty patients of carcinoma cervix FIGO Stage IIIB treated with concurrent chemoradiotherapy were selected for this study. The external contour of bones was delineated on planning CT as a surrogate for BM. We generated three plans on a single patient:1. without BM as the dose constraint, namely N-IMRT plan; 2. with BM constraint, namely BMS-IMRT plan; 3. VMAT plan in which BM constraint was given. The dose volume histogram (DVH) for planning target volume (PTV) and organs at risk (OAR) were analyzed. BM parameters: V10, V20, V30, V40, mean, maximum and minimum dose were compared.  Results: PTV coverage was comparable in all techniques. VMAT plans resulted in superior BM sparing compared with N-IMRT plan (P-<0.001) and BMS-IMRT plan (P-<0.001, 0.021 and 0.001 respectively for V20, V30 and V40). VMAT plans had better CI compared with BMS-IMRT (P-0.002) and N-IMRT (P-0.001) plans. CONCLUSION: Our study adds to the growing evidence that VMAT might be the preferred technique for patients with carcinoma of the cervix undergoing concurrent chemoradiotherapy, as it provides comparable target coverage and better sparing of bone marrow compared to IMRT.

Investigating the resistance mechanism of 5-fluorouracil in colorectal cancer based on surface markers of cancer stemness and cytokine level: A pre-clinical study.

BACKGROUND: Colorectal cancer (CRC) is the deadliest malignancy in the world. The first-line chemotherapy used for CRC is 5-fluorouracil (5-FU). 5-FU completely eradicates rapidly proliferating and terminally differentiated tumor cells but fails to target cancer stem cells (CSCs). As a result, the tumor may shrink temporarily, but remnant CSC multiplies and forms a tumor again more aggressively. The recurrence and resistance lead to metastasis. METHODOLOGY: CRC was induced in 12 Sprague-Dawley (RPCP/IAEC/2019-20/R2) rats by 1,2 dimethyl hydrazine. Later, animals were treated with 5-FU for 7 weeks at a 10 mg/kg dose by the subcutaneous route. At the end of treatment, half population was sacrificed (6), whereas the remaining half (6) was left without treatment of 5-FU for 5 weeks and then sacrificed. Parameters such as body weight, complete blood count (CBC), immune cell subset (CD4, CD8, and NK cells), colon length to weight index, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level, occult blood in stool, tumor multiplicity, and liver metastasis were estimated. In addition, the dissected colon was fixed in formalin and sent to the histology lab for hematoxylin-eosin staining and immunohistochemistry at both intervals. RESULTS: All blood and tissue-based markers have shown significant differences (p < 0.05) between the animals sacrificed at the end of the 27th week and the end of the 32nd week for 5-FU treatment. CONCLUSION: It can be concluded that 5-FU up-regulates inflammatory cytokines and cell surface markers of CSC that promote CRC stemness via the Wnt/ß-catenin pathway. Also, involvement of Nf-κB, fibronectin, MMP-9, and RANKL leads to tumorigenesis, disease aggressiveness, metastasis, and resistance.

Pre-Pulseless Takayasu Arteritis is Associated with Distinct Clinical and Angiographic Features but Similar Outcomes - A Cohort Study.

Objectives: To compare the presentation, angiographic features, evolution, and prognosis of prepulseless Takayasu arteritis (TAK) with TAK with pulse loss. Methods: Pre-pulseless TAK (defined as without pulse loss in the upper limbs, lower limb, carotid, or subclavian arteries) were identified from a cohort of TAK. Demographic characteristics, clinical features, angiographic involvement, baseline and longitudinal patterns of disease activity, medication use, and mortality rates were compared between pre-pulseless TAK and TAK with pulse loss. Adjusted odds ratios (aOR, with 95%CI) for categorical variables between pre-pulseless TAK and TAK with pulse loss were computed using multivariable-adjusted logistic regression models. Time-to-event data was compared using hazard ratios (HR) with 95%CI. Results: Compared with TAK with pulse loss, pre-pulseless TAK (91/238, 38.24%) more frequently had deranged renal function (aOR 4.43, 95%CI 1.58-12.37) and Hata's type IV disease (aOR 8.02, 95%CI 2.61-24.65), and less often had pulse or blood pressure asymmetry (aOR 0.34, 95%CI 0.18-0.63), limb claudication (aOR for upper limb 0.38, 95%CI 0.18-0.82, for lower limb 0.28, 95%CI 0.12-0.68), right subclavian (aOR 0.45, 95%CI 0.23-0.90) or left carotid artery involvement (aOR 0.42, 95%CI 0.21-0.84). Only two patients with pre-pulseless TAK developed pulse loss on follow-up. Despite fewer pre-pulseless TAK having active disease at presentation, similar proportions of patients in both groups had active disease on follow-up. Survival was similar in both groups (HR for mortality 0.41, 95%CI 0.09-1.90). Conclusion: Pulse loss on follow-up is uncommon in those with prepulseless TAK. Pre-pulseless TAK is associated with similar long-term outcomes to TAK with pulse loss.