Characterization and classification of ductal carcinoma tissue using four channel based stokes-mueller polarimetry and machine learning.

Interaction of polarized light with healthy and abnormal regions of tissue reveals structural information associated with its pathological condition. Even a slight variation in structural alignment can induce a change in polarization property, which can play a crucial role in the early detection of abnormal tissue morphology. We propose a transmission-based Stokes-Mueller microscope for quantitative analysis of the microstructural properties of the tissue specimen. The Stokes-Mueller based polarization microscopy provides significant structural information of tissue through various polarization parameters such as degree of polarization (DOP), degree of linear polarization (DOLP), and degree of circular polarization (DOCP), anisotropy (r) and Mueller decomposition parameters such as diattenuation, retardance and depolarization. Further, by applying a suitable image processing technique such as Machine learning (ML) output images were analysed effectively. The support vector machine image classification model achieved 95.78% validation accuracy and 94.81% testing accuracy with polarization parameter dataset. The study's findings demonstrate the potential of Stokes-Mueller polarimetry in tissue characterization and diagnosis, providing a valuable tool for biomedical applications.

Uncovering the Unknown: Granulomatous Peritonitis After Right Ovarian Cystectomy at a Tertiary Care Center in South India-A Case Report.

Background. Granulomatous peritonitis is a rare postoperative complication caused by a delayed hypersensitivity reaction to foreign substances. It can be challenging to diagnose owing to its vague presentations, and its possibility is often overlooked. Tubercular peritonitis and peritoneal carcinomatosis are the 2 crucial differential diagnoses that need to be taken into account. However, making a clinical differentiation between these 2 entities is challenging and necessitates a careful histopathological and microbiological analysis. Case Presentation. In this report, we present the case of a 28-year-old female who developed granulomatous peritonitis following a right ovarian cystectomy. The diagnosis was confirmed by histopathological examination. Conclusion. We must be aware of this rare entity, which, if left untreated, could have serious consequences, and consider its possibility in cases where the patient complains of abdominal pain after any abdominal procedure. We hope to provide insights into the importance of histopathological examination in aiding a confirmatory diagnosis of this entity.

Machine Learning Enabled Photoacoustic Spectroscopy for Noninvasive Assessment of Breast Tumor Progression In Vivo: A Preclinical Study.

Breast cancer is a dreaded disease affecting women the most in cancer-related deaths over other cancers. However, early diagnosis of the disease can help increase survival rates. The existing breast cancer diagnosis tools do not support the early diagnosis of the disease. Therefore, there is a great need to develop early diagnostic tools for this cancer. Photoacoustic spectroscopy (PAS), being very sensitive to biochemical changes, can be relied upon for its application in detecting breast tumors in vivo. With this motivation, in the current study, an aseptic chamber integrated photoacoustic (PA) probe was designed and developed to monitor breast tumor progression in vivo, established in nude mice. The device served the dual purpose of transporting tumor-bearing animals to the laboratory from the animal house and performing PA experiments in the same chamber, maintaining sterility. In the current study, breast tumor was induced in the nude mice by MCF-7 cells injection and the corresponding PA spectra at different time points (day 0, 5, 10, 15, and 20) of tumor progression in vivo in the same animals. The recorded photoacoustic spectra were subsequently preprocessed, wavelet-transformed, and subjected to filter-based feature selection algorithm. The selected top 20 features, by minimum redundancy maximum relevance (mRMR) algorithm, were then used to build an input feature matrix for machine learning (ML)-based classification of the data. The performance of classification models demonstrated 100% specificity, whereas the sensitivity of 95, 100, 92.5, and 85% for the time points, day 5, 10, 15, and 20, respectively. These results suggest the potential of PA signal-based classification of breast tumor progression in a preclinical model. The PA signal contains information on the biochemical changes associated with disease progression, emphasizing its translational strength toward early disease diagnosis.

Effect of a Submucosal Injection of Platelet-Rich Plasma on the Rate of Orthodontic Tooth Movement - A Split-Mouth, Single-Blind Randomized Controlled Trial.

Objective: To investigate the effect of submucosal injection of platelet-rich plasma (PRP) on the rate of mini-implant-supported retraction, using a split-mouth randomized clinical design. Materials and Methods: Twenty subjects of either gender between 16 and 25 years of age with bimaxillary dentoalveolar protrusion and crowding of <4 mm scheduled to undergo fixed mechanotherapy with the extraction of 1st premolars; were recruited for the study. Those with a periodontally compromised dentition, blood dyscrasias, smoking/alcoholism, or with a history of fixed orthodontic treatment were not considered. The intervention side received a submucosal injection of autologous PRP which was prepared using 10 ml of the patient's blood. The rate of extraction space closure on both sides was recorded and compared monthly for 3 months using a digital caliper. Results: Mean overall retraction was faster on the intervention side as compared to the control side by 1.5 times and was statistically significant with a P value of 0.001. There was no influence of gender on the rate of retraction. There was no reported swelling or discomfort associated with the PRP injection. Conclusions: Submucosal injection of PRP significantly accelerates orthodontic tooth movement and can therefore be used as an effective, safe, and minimally invasive method to expedite orthodontic treatment.

Gaussian Blurring Technique for Detecting and Classifying Acute Lymphoblastic Leukemia Cancer Cells from Microscopic Biopsy Images.

Visual inspection of peripheral blood samples is a critical step in the leukemia diagnostic process. Automated solutions based on artificial vision approaches can accelerate this procedure, while also improving accuracy and uniformity of response in telemedicine applications. In this study, we propose a novel GBHSV-Leuk method to segment and classify Acute Lymphoblastic Leukemia (ALL) cancer cells. GBHSV-Leuk is a two staged process. The first stage involves pre-processing, which uses the Gaussian Blurring (GB) technique to blur the noise and reflections in the image. The second stage involves segmentation using the Hue Saturation Value (HSV) technique and morphological operations to differentiate between the foreground and background colors, which improve the accuracy of prediction. The proposed method attains 96.30% accuracy when applied on the private dataset, and 95.41% accuracy when applied on the ALL-IDB1 public dataset. This work would facilitate early detection of ALL cancer.

Knowledge, attitude and practices towards COVID-19 among Indian medical undergraduates: a questionnaire-based study.

Background: The Coronavirus disease-19 (COVID-19) infection of severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) has emerged as a recent pandemic, increasing the need for epidemiological studies and studies on public health. Only some studies have evaluated the awareness of medical undergraduates in India and other countries, leading to a lack of literature. Methods: This study is a descriptive cross-sectional questionnaire-based study conducted in Kasturba Medical College, Mangalore, India, between June to August 2020. An online survey using Google Forms was circulated among undergraduate medical students in India by a convenient sampling method for data collection. Descriptive analysis was derived based on frequencies and percentages, and the association with age, gender, and year of undergraduate training medical course was derived using the chi-square test. Results: Altogether, 630 students from India responded to the survey, with a maximum response from students studying in the second year (38.7%). Nearly 63.85% of responders identified themselves as females. Knowledge regarding the human-to-human transmission of the virus, symptoms, complications, definition of "close contact, quarantine, and its indications was adequate among the students, with more than 70% correct responses. However, one-fourth of the students needed to gain more knowledge about masks. Respiratory hygiene was poor among 24.8%. Nearly 40% of students were unaware of the management of patients with COVID-19. Conclusion: There is a need for regular quality training and institutional programs on infection control of COVID-19 and other infectious diseases across all Indian medical colleges to educate undergraduate medical students, who are future healthcare professionals, thus minimizing the risk of transmission and providing standardized care for patients.

Study of significance of bone marrow microvessel density in myeloproliferative neoplasms in correlation with CD34 blasts, mast cell count and fibrosis.

Background: Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell diseases characterised by myeloid cell growth from one or more lineages. Angiogenesis, in contrast to other subtypes, plays a substantial role in the pathophysiology of primary myelofibrosis (PMF). Research expressing the correlation of microvessel density (MVD), blasts, fibrosis and mast cell count in MPN cases are rarely conducted. We aimed to study the significance of MVD in correlation with CD34 blasts, mast cells and fibrosis in bone marrow biopsies of MPN patients. Methods: The current research was a cross sectional study conducted on 66 cases diagnosed as MPN during a six-year period. This comprised of 32 chronic myeloid leukemia (CML), 31 PMF and three essential thrombocythemia (ET) cases. Routine staining along with reticulin stain to look for fibrosis and immunohistochemistry (IHC) using CD34 and mast cell tryptase (MCT) were performed. Results: We found increased MVD in PMF, when compared to CML and ET (p = 0.042). Further, mean MVD was observed to be increased with high blast counts (p = 0.036). On follow up, raised mean MVD was seen in those cases with relapse/deceased as compared to disease-free patients, which was highly significant (p = 0.000). Conclusions: Increased MVD score was mostly associated with PMF subtype among all the MPNs. Further, higher MVD was observed to be associated with increased blast count and poor prognosis. With angiogenesis playing a critical role in disease outcome, we now have drugs to regulate angiogenesis that are supported by contemporary research. However, further studies with larger cohorts to establish the theranostic role of MVD in MPNs is recommended.

Pre-University Health Professional Students' Readiness and Perception Toward Interprofessional Education.

Background: Interprofessional education (IPE) helps preparing the learners in all healthcare professions to work effectively in collaborative teams. This study was undertaken to assess the readiness and perception of IPE of preuniversity health professional students even before they enter their health professional courses. Methods: The preuniversity health professional students along with final-year medical and dental students were recruited for the study. The readiness for interprofessional learning scale was used to measure the student's readiness toward IPE before the interprofessional-related activity session. The preuniversity students also completed the IEPS scale after their interaction with final-year medical and dental students. Results: Most of the aspiring health professional students during their foundation year expressed positive attitude toward readiness for IPE. Most preuniversity students realized that by learning with various professional students would make them effective member of healthcare team. The students had positive perception toward competence and autonomy, perceived need for cooperation, perception of actual cooperation, and understanding other's value, which were significantly higher from score 3 of somewhat disagree (P < 0.001). Conclusion: Most of the aspiring health professional students in their preuniversity year expressed positive attitude toward readiness for IPE although were not prepared to take roles and responsibility within the interprofessional group. They could well perceive the need for cooperation, perception of actual cooperation, and understanding other's value while working in an IP team.

Clinico-histopathological Profile of Primary Paediatric Intra-abdominal Tumours: a Multi-hospital-Based Study.

Paediatric cancers are gradually on the rise in India. Its proportion among children aged < 15 years constitutes close to 5% of the total cancer affected population. A high proportion of this constitutes intra-abdominal tumours. This study was done to study the demographic profile, clinical features and management of intra-abdominal tumours among children. Data of all histopathologically confirmed patients aged < 15 years with various primary intra-abdominal tumours diagnosed from 2009 to 2019 were included in this study. The median age of the patients (n = 50) was 3 years (IQR 1.4, 6). The median age at diagnosis of cancer (n = 23) was 2.5 years (IQR 1, 4). Tumours were more common among males (70%). The most common tumour in this study was Wilm's tumour (17 (34%)). Forty-eight (96%) patients had malignant tumours. Fever was present among the majority (27 (54%)) of the patients. The most common anti-cancer drug used for management was Vincristine, used among 23 patients. Remission was more among infants with Wilm's tumour (P = 0.0221) and among patients with Hodgkin's lymphoma (HL) (P = 0.0444). Default with treatment was more among patients with stage 4 malignancy (P = 0.0186). Recovery following treatment was more among patients with germ cell tumour (P = 0.0082). Reasons for default with treatment in the late stages of malignancies need to be identified in future research studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-021-01365-x.

Exploring photoacoustic spectroscopy-based machine learning together with metabolomics to assess breast tumor progression in a xenograft model ex vivo.

In the current study, a breast tumor xenograft was established in athymic nude mice by subcutaneous injection of the MCF-7 cell line and assessed the tumor progression by photoacoustic spectroscopy combined with machine learning tools. The advancement of breast tumors in nude mice was validated by tumor volume kinetics and histopathology and corresponding image analysis by TissueQuant software compared to controls. The ex vivo tumors in progressive conditions belonging to time points, day 5th, 10th, 15th & 20th, were excited with 281 nm pulsed laser light and recorded the corresponding photoacoustic spectra in time domain. The spectra were then pre-processed, augmented for a 10-fold increase in the data strength, and subjected to wavelet packet transformation for feature extraction and selection using MATLAB software. In the present study, the top 10 features from all the time point groups under study were selected based on their prediction ranking values using the mRMR algorithm. The chosen features of all the time-point groups were then subjected to multi-class Support Vector Machine (SVM) algorithms for learning and classifying into respective time point groups under study. The analysis demonstrated accuracy values of 95.2%, 99.5%, and 80.3% with SVM- Radial Basis Function (SVM-RBF), SVM-Polynomial & SVM-Linear, respectively. The serum metabolomic levels during tumor progression complemented photoacoustic patterns of tumor progression, depicting breast cancer pathophysiology.

Cysts that Still Persist: A Case Series of Cysticercosis on Histopathological Evaluation.

Cysticercus is the infective larval form of the cystode T. solium that causes cysticercosis. It is has been declared as one of the neglected endemic zoonoses by the WHO. Poor sanitation, and consumption of undercooked infected pork and raw vegetables contaminated by human feces are the potential sources. Cysticercosis can affect various organs. India is one of the endemic countries where the parasite is prevalent in many states. This study aimed to analyze and report cases of cysticercosis based on the histopathological diagnosis. This is a retrospective study that included cases which had been reported as cysticercosis on histopathology from 2010 to 2018 at a tertiary care hospital. The clinical presentation of these cases along with macroscopic and microscopic features were reviewed. There were six cases of cysticercosis that were diagnosed on histopathology during the study period. Among them, two cases were intramuscular lesions, three were subcutaneous, and one case was an intraventricular lesion in the brain. Three of the cases presented as cystic lesions. On histopathological evaluation, cysts were identified in four cases on macroscopy. Microscopically, the cross section of the cysticercus was seen in all six cases with associated inflammatory change. To conclude, cysticercosis can clinically present as a benign neoplastic or an inflammatory lesion. Microscopic findings dictate the diagnosis of cysticercosis, although histopathological evaluation is not common.

Pebbled Trachea: A Case Series and Literature Review of Tracheobronchopathia Osteochondroplastica.

We report a series of three cases diagnosed with tracheobronchopathia osteochondroplastica on bronchoscopy and computed tomography (CT) chest. Most patients were diagnosed incidentally on evaluation for chronic cough. The association of this entity with chronic bacterial infections and tuberculosis is an intriguing entity that was observed in our patients. Nodular, ulcerative, and calcific lesions in the trachea are bronchoscopic findings seen in quite a few other conditions posing diagnostic challenges. However, the classical bronchoscopic appearance with CT imaging in an appropriate clinical context can lead to an accurate diagnosis of this condition. We describe this array of cases with varying clinical presentations, their associations, and deliberate the literature reviews on this rare entity.

Guidelines for various laboratory sections in view of COVID-19: Recommendations from the Indian Association of Pathologists and Microbiologists.

Declared as a pandemic by WHO on March 11, 2020, COVID-19 has brought about a dramatic change in the working of different laboratories across the country. Diagnostic laboratories testing different types of samples play a vital role in the treatment management. Irrespective of their size, each laboratory has to follow strict biosafety guidelines. Different sections of the laboratory receive samples that are variably infectious. Each sample needs to undergo a proper and well-designed processing system so that the personnel involved are not infected and also their close contacts. It takes a huge effort so as to limit the risk of exposure of the working staff during the collection, processing, reporting or dispatching of biohazard samples. Guidelines help in preventing the laboratory staff and healthcare workers from contracting the disease which has a known human to human route of transmission and high rate of mortality. A well-knit approach is the need of the hour to combat this fast spreading disease. We anticipate that the guidelines described in this article will be useful for continuing safe work practices by all the laboratories in the country.

A Quest for Accuracy: Evaluation of The Paris System in Diagnosis of Urothelial Carcinomas.

INTRODUCTION: Urine cytology is an important screening tool of patients for urothelial carcinoma (UC) and follow-up of patients with treated disease. Ease of procurement, cost-effectiveness, and lower turnaround time are the major advantages. OBJECTIVE: To compare current system of reporting (CSR) at our institute with The Paris System (TPS) and analyze utility of urine cytology based on TPS reporting in correlation with urine culture and histopathology. MATERIALS AND METHODS: One-year retrospective study of 90 cases was undertaken wherein cases presenting with painless hematuria and clinically suspicious of UC were included. Urine cytology slides were reviewed and reported with TPS guidelines. These findings were correlated with histopathological diagnosis and urine culture as indicated. Statistical analysis was done using SPSS 17 software. RESULTS: With TPS guidelines, 11.1% and 5.6% cases were reported as high-grade UC (HGUC) and low-grade urothelial neoplasm (LGUN), respectively. Suspicious for HGUC category included 17.8% of cases. The rate of reporting "atypical urothelial cells (AUC)" was significantly lower (11.1%) with TPS on comparison with CSR (16.7%). Histopathological correlation of positive predictive value for HGUC was better (100%) on using TPS when compared with CSR (64.3%). Among 11 cases with microbial growth on urine culture, 9.1% were reported as atypical. Sensitivity and accuracy of TPS in detecting UC were 83.3% and 86.52%, respectively. Both were higher when compared with CSR. CONCLUSION: In comparison to CSR, criteria of TPS limit the AUC category and enhance the sensitivity and accuracy of detecting HGUC. Adopting TPS for urinary cytology will ensure uniformity and accuracy of HGUC diagnosis.

A Study of Pap Smears in HIV-Positive and HIV-Negative Women from a Tertiary Care Center in South India.

OBJECTIVES: The aim of this work was to study the spectrum of epithelial abnormalities on Pap smears of HIV-positive women categorized as per the Bethesda System of Reporting Cervical Cytology, to correlate them with CD4 lymphocyte counts, and to compare them with the spectrum of abnormalities seen in a HIV-negative control group. Study Design and Methodology: The present study was a 6-year retrospective study conducted in the Department of Pathology at Kasturba Medical College, Mangalore, which included 150 Pap smears from HIV-positive and HIV-negative women, respectively. The Pap-stained slides of the cases were retrieved and studied. The data collected were tabulated and analyzed. A statistical study was performed using SPSS software. The χ2 test was used to analyze the data and a p value < 0.05 was considered to be significant. RESULTS: Pap smear abnormalities were twice as high in HIV-infected women (12%) as compared with HIV-negative women (6%; p = 0.006, RR = 2). Negative for intraepithelial lesion/malignancy was the most common finding (88%), which was further subdivided into inflammatory, atrophic smear, non-specific, candidiasis, and bacterial vaginitis groups. The percentage of epithelial abnormalities was 12%, including: atypical squamous cells of undetermined significance, 5.55%; atypical squamous cells, cannot exclude HSIL, 16.66%; low-grade squamous intraepithelial lesion, 5.55%; high-grade squamous intraepithelial lesion (HSIL), 61.11%, and squamous cell carcinoma, 11.11%. The highest incidence of intraepithelial lesions in HIV-positive females was in the age group of 34-49 years. CD4 cell counts fell in the range of 200-500 cells/mm3 in most of the HIV-positive patients (68.75%), but was not found to be statistically significant. CONCLUSION: Routine Pap smear examination is advocated in women with HIV as the prevalence of epithelial cell abnormalities was found to be 12%, which was twice as high as compared to the HIV-negative control group. Although there was no correlation of epithelial cell abnormalities with CD4 counts, a higher rate of the cases with epithelial abnormalities were observed to have CD4 cell counts of 200-500 cells/mm3.

Image Findings of Solid Pseudopapillary Neoplasms of the Pancreas on Multiphasic Multidetector CT Scan-A Single Institute Experience from Southern India.

INTRODUCTION: Solid Pseudopapillary Neoplasms (SPN) are uncommon pancreatic tumours and are slow growing with uncertain malignant potential, showing female preponderance. Postoperative prognosis is good and metastasis is rare. AIM: To summarise the imaging and pathological features of seven cases of SPN in three years period, from January 2013 to January 2016. MATERIALS AND METHODS: In this retrospective study the imaging features of seven cases on triphasic multidetector Computed Tomogram (CT), a 16-slice scanner, were reviewed along with CT-guided Fine Needle Aspiration Cytology (FNAC) and histopathological examination. Statistics were expressed in terms of percentiles. RESULTS: All cases were female patients with an age range of 13-35 years (mean: 23.3 years). On CT assessment, the size of the tumours varied from 2.5-14 cm (mean: 5.3 cm). All these tumours were well capsulated and round to oval in shape. In four out of seven cases, the tumour was located in the tail of pancreas. All the solid enhancing portions showed moderate enhancement of at least 20-30 HU compared to unenhanced scan, on the other hand the cystic parts remained unenhanced with <5 HU variation in comparison to the plain scan. Histopathological examination exhibited characteristic poorly cohesive cuboidal cells arranged in papillaroid pattern having fine nuclear chromatin with nuclear grooves. CONCLUSION: Solid pseudopapillary neoplasm is a high diagnostic possibility in case of a young female having pancreatic mass and needs to be evaluated with triphasic contrast enhanced CT scan, followed by FNAC and or histopathological examination.

Histomorphologic Spectrum in Hyaline Vascular Variant of Castleman Disease.

INTRODUCTION: Castleman Disease (CD) is a rare lymphopro-liferative disorder with heterogenous clinical and pathological features. It is a rare disease with mention in the rare disease data of the orphanet. It can present as unicentric or multicentric disease. Hyaline vascular variant and plasma cell variant are the two pathological subtypes. Hyaline vascular variant accounts for nearly 80% to 90% of unicentric cases. Hyaline vascular subtype variant has follicular and stroma rich subtype. AIM: To study the histomorphologic spectrum of hyaline vascular variant of CD. MATERIALS AND METHODS: Retrospective cross-sectional, observational study was undertaken from the archival data between January 2009 and April 2015. Only ten cases of hyaline vascular CD were identified after studying the histomorphological characteristics. Both follicular and interfollicular changes were studied in detail. RESULTS: The age of presentation ranged from 17 years to 59 years. Seven out of 10 cases were female. Site of presentation included cervical, inguinal, retroperitoneal, intra-abdominal and axillary. Six cases showed predominant follicular change. Two cases were sclerotic subtype. Two cases showed both follicular and interfollicular changes in equal proportion. Distribution of follicles throughout the lymphnode was seen in eight cases. Uniform sized follicles seen in seven out of ten cases. Small germinal centre with lymphocyte depletion was one of the uniform features seen in all 10 cases. Numerous high endothelial vessels were seen in nine cases. Twinning of germinal centre was seen in two cases. All ten cases showed concentric rings of small lymphocytes. Lollipop pattern was relatively rare feature seen in only two cases. CONCLUSION: Hyaline vascular variant of CD has considerable morphologic variation with few consistent features seen in most of the cases.

Megakaryocytic morphology in Janus kinase 2 V617F positive myeloproliferative neoplasm.

CONTEXT: Alterations in megakaryocyte morphology are the hallmark of myeloproliferative neoplasms (MPNs). These neoplasm are also associated with Janus kinase 2 (JAK2) V617F mutation in nearly 95% patients with polycythemia vera (PV), 40% patients of essential thrombocythemia (ET) and 50% patients of myelofibrosis (MF). The utility of megakaryocyte morphology in these disorders in correlation with JAK2 V617F remains unresolved. AIMS: The aim of the study was to assess the morphology of megakaryocytes in bone marrow aspirates (BMAs) and bone marrow biopsies of patients of BCR-ABL negative MPNs with JAK2 V617F mutation. SETTINGS AND DESIGN: This study was a retrospective and prospective, hospital-based study undertaken for a period ranging from January 2011 to April 2015. SUBJECTS AND METHODS: Assessment of morphological features of megakaryocytes in 15 BMAs and their respective biopsies which included seven cases of PV, three cases of ET, and five cases of MF with JAK2 V617F mutation. STATISTICAL ANALYSIS USED: Chi-square test and Fisher exact test were used to compare the different features of megakaryocytes. Software version SPSS 13.0 was used. RESULTS: Megakaryocytes in ET were found to have characteristically large size with staghorn multinucleated nuclei and exhibiting large amount of cytoplasm. MF showed dense clustering of megakaryocytes with staghorn nucleus along with sinusoidal dilatation and intrasinusoidal hematopoiesis. PV showed loose and dense clustering of megakaryocytes with a predominance of cloud-like nuclei. Few of the megakaryocytic morphologic features showed overlap between MF and PV and between ET and early MF. CONCLUSIONS: Megakaryocytic morphology can aid in the accurate diagnosis of the different subcategories of MPNs. This would help in categorization of clinically suspicious patients of JAK2 V617F negative patients.

A polymeric temozolomide nanocomposite against orthotopic glioblastoma xenograft: tumor-specific homing directed by nestin.

The development of effective therapeutic strategies for glioblastoma faces challenges such as modulating the blood brain barrier (BBB) for drug influx and selectively targeting tumor cells. Nanocarrier drug delivery strategies are functionalized to enhance vascular permeability. We engineered superparamagnetic iron oxide nanoparticle (SPION) based polymeric nanocomposites (84.37 ± 12.37 nm / 101.56 ± 7.42 nm) embedding temozolomide (TMZ) targeted against glioblastoma by tagging an antibody against nestin, a stem cell marker, and transferrin / polysorbate-80 to permeate the BBB. The targeting and therapeutic efficacy of the nanocomposite resulted in enhanced permeability across the BBB in an orthotopic glioblastoma xenograft model. Sustained release of TMZ from the nanocomposite contributed to enhanced tumor cell death while sparing normal brain cells as evidenced through micro SPECT/CT analysis. The functionalized nanocomposites showed significant reductions in tumor volume compared to pure TMZ, as substantiated by reduced proliferation markers such as proliferating cell nuclear antigen (PCNA) and Ki-67. We report here a novel targeted TMZ delivery strategy using a potent homing moiety, nestin, tagged to a polymeric nanocomposite to target glioblastoma. In addition to tumor targeting, this study constitutes a broad horizon for enhanced therapeutic efficacy with further scope for capitalizing on the magnetic properties of SPION for targeted killing of cancer cells while sparing normal tissues.

Enhanced effect of geldanamycin nanocomposite against breast cancer cells growing in vitro and as xenograft with vanquished normal cell toxicity.

Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity. The particle size of nanocomposite was ascertained to be 76±10nm with acceptable stability. A comparative dose dependent in vitro validation of cytotoxicity showed an enhanced cellular damage and necrosis in breast cancer (MCF-7) cell line at a low dose of 5.49nM (in GDM nanocomposite) in contrast to 20nM of pure GDM, while normal breast epithelial cells (MCF-10A) were least affected. Besides, in vivo study (in breast cancer xenografts) substantiated 2.7 fold delay in tumor progression mediated by redundancy in the downstream functions of p-Akt and MAPK-Erk leading to apoptosis with negligible hepatotoxicity. Pure GDM disrupted the function and morphology of liver with lesser therapeutic efficacy than the GDM nanocomposite. These findings deduce that GDM based polymeric magnetite nanocomposite play a vital role in efficacious therapy while vanquishing normal cells and hepatic toxicity and thereby promising it to be reinstated in clinics.