Search results for: cancer genomics

Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

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Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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Authors: Andy Ho

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Breast cancer is a common cancer in Australia. Early diagnosis is crucial for improving patient outcomes, as later-stage detection correlates with poorer prognoses. While multiparametric MRI offers superior sensitivity in detecting invasive and high-grade breast cancers compared to conventional mammography, its extended scan duration and high costs limit widespread application. As a result, full protocol MRI screening is typically reserved for patients at elevated risk. Recent advancements in imaging technology have facilitated the development of Abbreviated MRI protocols, which dramatically reduce scan times (<10 minutes compared to >30 minutes for full protocol). The potential for Abbreviated MRI to offer a more time- and cost-efficient alternative has implications for improving patient accessibility, reducing appointment durations, and enhancing compliance—especially relevant for individuals requiring regular annual screening over several decades. The purpose of this study is to assess the diagnostic efficacy of Abbreviated MRI for breast cancer screening among high-risk patients at the Royal Prince Alfred Hospital (RPA). This study aims to determine the sensitivity, specificity, and inter-reader variability of Abbreviated MRI protocols when interpreted by subspecialty-trained Breast Radiologists. A systematic review of the RPA’s electronic Picture Archive and Communication System identified high-risk patients, defined by Australian ‘Medicare Benefits Schedule’ criteria, who underwent Breast MRI from 2021 to 2022. Eligible participants included asymptomatic patients under 50 years old referred by the High-Risk Clinic due to a high-risk genetic profile or relevant familial history. The MRIs were anonymized, randomized, and interpreted by four Breast Radiologists, each independently completing standardized proforma evaluations. Radiological findings were compared against histopathology as the gold standard or follow-up imaging if biopsies were unavailable. Statistical metrics, including sensitivity, specificity, and inter-reader variability, were assessed. The Fleiss-Kappa analysis demonstrated a fair inter-reader agreement (kappa = 0.25; 95% CI: 0.19–0.32; p < 0.0001). The sensitivity for detecting malignancies was 0.75, with a specificity of 0.84. These findings underline the potential of Abbreviated MRI as a reliable screening tool for malignancies with significant specificity, though reduced sensitivity highlights the importance of robust radiologist training and consistent evaluation standards. Abbreviated MRI protocols exhibit promise as a viable screening option for high-risk patients, combining reduced scan times and acceptable diagnostic accuracy. Further work to refine interpretation practices and optimize training is essential to maximize the protocol’s utility in routine clinical screening and facilitate broader accessibility.

Keywords: abbreviated, breast, cancer, MRI

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Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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Authors: James Jr. Mashiyane, Risuna Nkolele, Stephanie J. Müller, Gciniwe S. Dlamini, Rebone L. Meraba, Darlington S. Mapiye

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When performing language tasks in natural language processing (NLP), the dimensionality of word embeddings is chosen either ad-hoc or is calculated by optimizing the Pairwise Inner Product (PIP) loss. The PIP loss is a metric that measures the dissimilarity between word embeddings, and it is obtained through matrix perturbation theory by utilizing the unitary invariance of word embeddings. Unlike in natural language, in genomics, especially in genome sequence processing, unlike in natural language processing, there is no notion of a “word,” but rather, there are sequence substrings of length k called k-mers. K-mers sizes matter, and they vary depending on the goal of the task at hand. The dimensionality of word embeddings in NLP has been studied using the matrix perturbation theory and the PIP loss. In this paper, the sufficiency and reliability of applying word-embedding algorithms to various genomic sequence datasets are investigated to understand the relationship between the k-mer size and their embedding dimension. This is completed by studying the scaling capability of three embedding algorithms, namely Latent Semantic analysis (LSA), Word2Vec, and Global Vectors (GloVe), with respect to the k-mer size. Utilising the PIP loss as a metric to train embeddings on different datasets, we also show that Word2Vec outperforms LSA and GloVe in accurate computing embeddings as both the k-mer size and vocabulary increase. Finally, the shortcomings of natural language processing embedding algorithms in performing genomic tasks are discussed.

Keywords: word embeddings, k-mer embedding, dimensionality reduction

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Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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Authors: Mónica P. Cala, Juan S. Carreño, Roland J.W. Meesters

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Recently, collection of biological fluids on special filter papers has become a popular micro-sampling technique. Especially, the dried blood spot (DBS) micro-sampling technique has gained much attention and is momently applied in various life sciences reserach areas. As a result of this popularity, DBS are not only intensively competing with the venous blood sampling method but are at this moment widely applied in numerous bioanalytical assays. In particular, in the screening of inherited metabolic diseases, pharmacokinetic modeling and in therapeutic drug monitoring. Recently, microsampling techniques were also introduced in “omics” areas, whereunder metabolomics. For a metabolic profiling study we applied micro-sampling of biological fluids (blood and plasma) from healthy controls and from women with breast cancer. From blood samples, dried blood and plasma samples were prepared by spotting 8uL sample onto pre-cutted 5-mm paper disks followed by drying of the disks for 100 minutes. Dried disks were then extracted by 100 uL of methanol. From liquid blood and plasma samples 40 uL were deproteinized with methanol followed by centrifugation and collection of supernatants. Supernatants and extracts were evaporated until dryness by nitrogen gas and residues derivated by O-methyxyamine and MSTFA. As internal standard C17:0-methylester in heptane (10 ppm) was used. Deconvolution and alignment of and full scan (m/z 50-500) MS data were done by AMDIS and SpectConnect (http://spectconnect.mit.edu) software, respectively. Statistical Data analysis was done by Principal Component Analysis (PCA) using R software. The results obtained from our preliminary study indicate that the use of dried blood/plasma on paper disks could be a powerful new tool in metabolic profiling. Many of the metabolites observed in plasma (liquid/dried) were also positively identified in whole blood samples (liquid/dried). Whole blood could be a potential substitute matrix for plasma in Metabolomic profiling studies as well also micro-sampling techniques for the collection of samples in clinical studies. It was concluded that the separation of the different sample methodologies (liquid vs. dried) as observed by PCA was due to different sample treatment protocols applied. More experiments need to be done to confirm obtained observations as well also a more rigorous validation .of these micro-sampling techniques is needed. The novelty of our approach can be found in the application of different biological fluid micro-sampling techniques for metabolic profiling.

Keywords: biofluids, breast cancer, metabolic profiling, micro-sampling

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Authors: Geir Kirkebøen

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Most patients with serious diagnoses want to know their prognosis, in particular their expected survival time. As part of the informed consent process, physicians are legally obligated to communicate such information to patients. However, there is no established (evidence based) ‘best practice’ for how to do this. The two questions explored in this study are: How do physicians communicate expected survival time to patients, and how should it be done? We explored the first, descriptive question in a study with Norwegian oncologists as participants. The study had a scenario and a survey part. In the scenario part, the doctors should imagine that a patient, recently diagnosed with a serious cancer diagnosis, has asked them: ‘How long can I expect to live with such a diagnosis? I want an honest answer from you!’ The doctors should assume that the diagnosis is certain, and that from an extensive recent study they had optimal statistical knowledge, described in detail as a right-skewed survival curve, about how long such patients with this kind of diagnosis could be expected to live. The main finding was that very few of the oncologists would explain to the patient the variation in survival time as described by the survival curve. The majority would not give the patient an answer at all. Of those who gave an answer, the typical answer was that survival time varies a lot, that it is hard to say in a specific case, that we will come back to it later etc. The survey part of the study clearly indicates that the main reason why the oncologists would not deliver the mortality prognosis was discomfort with its uncertainty. The scenario part of the study confirmed this finding. The majority of the oncologists explicitly used the uncertainty, the variation in survival time, as a reason to not give the patient an answer. Many studies show that patients want realistic information about their mortality prognosis, and that they should be given hope. The question then is how to communicate the uncertainty of the prognosis in a realistic and optimistic – hopeful – way. Based on psychological research, our hypothesis is that the best way to do this is by explicitly describing the variation in survival time, the (usually) right skewed survival curve of the prognosis, and emphasize to the patient the (small) possibility of being a ‘lucky outlier’. We tested this hypothesis in two scenario studies with lay people as participants. The data clearly show that people prefer to receive expected survival time as a median value together with explicit information about the survival curve’s right skewedness (e.g., concrete examples of ‘positive outliers’), and that communicating expected survival time this way not only provides people with hope, but also gives them a more realistic understanding compared with the typical way expected survival time is communicated. Our data indicate that it is not the existence of the uncertainty regarding the mortality prognosis that is the problem for patients, but how this uncertainty is, or is not, communicated and explained.

Keywords: cancer patients, decision psychology, doctor-patient communication, mortality prognosis

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Authors: Shiva Rezaei, Seyed Jalal Hosseinimehr, Abbasali Karimpour Malekshah, Mansooreh Mirzaei, Fereshteh Talebpour Amiri, Mehryar Zargari

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Objective(s): Cyclophosphamide (CP), as an antineoplastic drug, is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA), as a natural phenylpropanoid, has antioxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Keywords: apoptosis, cyclophosphamide, liver injury, inflammation, oxidative stress, sinapic acid

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Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.

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After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).

Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS

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Authors: S. Zith Dey Babu, S. Kour, S. Verma, C. Verma, V. Pathania, A. Agrawal, V. Chaudhary, A. Manoj Puthur, R. Goyal, A. Pal, T. Danti Dey, A. Kumar, K. Wadhwa, O. Ved

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Background: Skin cancer is now is the buzzing button in the field of medical science. The cyst's pandemic is drastically calibrating the body and well-being of the global village. Methods: The extracted image of the skin tumor cannot be used in one way for diagnosis. The stored image contains anarchies like the center. This approach will locate the forepart of an extracted appearance of skin. Partitioning image models has been presented to sort out the disturbance in the picture. Results: After completing partitioning, feature extraction has been formed by using genetic algorithm and finally, classification can be performed between the trained and test data to evaluate a large scale of an image that helps the doctors for the right prediction. To bring the improvisation of the existing system, we have set our objectives with an analysis. The efficiency of the natural selection process and the enriching histogram is essential in that respect. To reduce the false-positive rate or output, GA is performed with its accuracy. Conclusions: The objective of this task is to bring improvisation of effectiveness. GA is accomplishing its task with perfection to bring down the invalid-positive rate or outcome. The paper's mergeable portion conflicts with the composition of deep learning and medical image processing, which provides superior accuracy. Proportional types of handling create the reusability without any errors.

Keywords: computer-aided system, detection, image segmentation, morphology

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

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Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

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Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

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Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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Authors: Elham Mansouri, Asghar Mesbahi

Abstract:

Purpose: In the current study, we aimed to investigate the macroscopic and microscopic dose enhancement effect of metallic nanoparticles in interstitial brachytherapy of uterus cancer by Iodin-125 source using a nano-lattice model in MCNPX (5) and MCNP6.1 codes. Materials and methods: Based on a nano-lattice simulation model containing a radiation source and a tumor tissue with cellular compartments loaded with 7mg/g spherical nanoparticles (bismuth, gold, and gadolinium), the energy deposited by the secondary electrons in microscopic and macroscopic level was estimated. Results: The results show that the values of macroscopic DEF is higher than microscopic DEF values and the macroscopic DEF values decreases as a function of distance from the brachytherapy source surface. Also, the results revealed a remarkable discrepancy between the DEF and secondary electron spectra calculated by MCNPX (5) and MCNP6.1 codes, which could be justified by the difference in energy cut-off and electron transport algorithms of two codes. Conclusion: According to the both MCNPX (5) and MCNP6.1 outputs, it could be concluded that the presence of metallic nanoparticles in the tumor tissue of uteruscancer increases the physical effectiveness of brachytherapy by I-125 source. The results presented herein give a physical view of radiosensitization potential of different metallic nanoparticles and could be considered in design of analytical and experimental radiosensitization studies in tumor regions using various radiotherapy modalities in the presence of heavy nanomaterials.

Keywords: MCNPX, MCNP6, nanoparticle, brachytherapy

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Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

Abstract:

Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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Authors: Sarah A. Alotaibi, Mohammed A. Almutairi, Abdullah A. Alsayari, Adibah M. Almutairi, Somaiah K. Almubayedh

Abstract:

Concerns over the presence of acrylamide in food date back to 2002, when Swedish scientists stated that, in carbohydrate-rich foods, amounts of acrylamide were formed when cooked at high temperatures. Similar findings were reported by other researchers which, consequently, caused major international efforts to investigate dietary exposure and the subsequent health complications in order to properly manage this issue. Due to this issue, in this work, we aim to determine the acrylamide level in different foods (coffee, potato chips, biscuits, and baby food) commonly consumed by the Saudi population. In a total of forty-three samples, acrylamide was detected in twenty-three samples at levels of 12.3 to 2850 µg/kg. In reference to the food groups, the highest concentration of acrylamide was found in coffee samples (<12.3-2850 μg/kg), followed by potato chips (655-1310 μg/kg), then biscuits (23.5-449 μg/kg), whereas the lowest acrylamide level was observed in baby food (<14.75 – 126 μg/kg). Most coffee, biscuits and potato chips products contain high amount of acrylamide content and also the most commonly consumed product. Saudi adults had a mean exposure of acrylamide for coffee, potato, biscuit, and cereal (0.07439, 0.04794, 0.01125, 0.003371 µg/kg-b.w/day), respectively. On the other hand, exposure to acrylamide in Saudi infants and children to the same types of food was (0.1701, 0.1096, 0.02572, 0.00771 µg/kg-b.w/day), respectively. Most groups have a percentile that exceeds the tolerable daily intake (TDI) cancer value (2.6 µg/kg-b.w/day). Overall, the MOE results show that the Saudi population is at high risk of acrylamide-related disease in all food types, and there is a chance of cancer risk in all age groups (all values ˂10,000). Furthermore, it was found that in non-cancer risks, the acrylamide in all tested foods was within the safe limit (˃125), except for potato chips, in which there is a risk for diseases in the population. With potato and coffee as raw materials, additional studies were conducted to assess different factors, including temperature, cocking time, and additives affecting the acrylamide formation in fried potato and roasted coffee, by systematically varying processing temperatures and time values, a mitigation of acrylamide content was achieved when lowering the temperature and decreasing the cooking time. Furthermore, it was shown that the combination of the addition of chitosan and NaCl had a large impact on the formation.

Keywords: risk assessment, dietary exposure, MOA, acrylamide, hazard

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Authors: Somit Dutta, Pallab Kar, Arnab Kumar Chakraborty, Arnab Sen, Tapas Kumar Chaudhuri

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In the present study three species of Clerodendrum; Clerodendrum indicum, Volkameria inermis and Clerodendrum colebrookianum were used to investigate the possible activity against oxidative stress. A detailed in-vivo and in-vitro antioxidant profiling, directly associated with inflammation-related carcinogenesis, has been executed with a motive to evaluate the free radical scavenging activity of Clerodendrum extract. Measurement of cell viability and ROS generation in HEK-293 (Human Embryonic Kidney Cell Line) cells was also estimated. The immune cell proliferative properties (MTT) and in-vitro assay for evaluation of their antioxidant activities including hydroxyl radical, nitric oxide, singlet oxygen, peroxinitrate and hydrogen peroxide, etc. were investigated. GC-MS and FTIR analyses have been performed to identify the active biological compounds. These active biological compounds were further studied to assess their potential medicinal properties, aided by molecular docking and interaction analysis between the active compounds and different proteins related to oxidative stress leading to progression of carcinogenesis. The research article clearly demonstrates the role of ROS in various phases of carcinogenesis. Therefore, the antioxidant and free radical scavenging capacity of all the Clerodendrum species might prove beneficial for the immune system. It might be concluded that this plant species offers great promise for cancer prevention and therapy due to the presence of several bioactive compounds and potent antioxidant capacity of C. colebrookianum.

Keywords: antioxidant, cancer, oxidative stress, reactive oxygen species (ROS)

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: Puneet Goyal, Aarti Agarwal

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Background and Objective: Nutritional support is an integral part of palliative care of advanced non-resectable abdominal malignancy patients, though is frequently neglected aspect. Non-Healing high output Entero-cutaneous fistulas sometimes require long term parenteral nutrition, to take care of catabolism and replacement of nutrients. We present a case of inoperable pancreatic malignancy with high output entero-cutaneous fistula, which was provided parenteral nutritional support with the use of Totally Implantable Venous Access Device (TIVAD). Method and Results: 55 year old man diagnosed with carcinoma pancreas had developed high entero-cutaneous fistula. His tumor was found to be inoperable and was on total parenteral nutrition through routine central line. This line was difficult to maintain as he required it for a long term TPN. He was planned to undergo Totally Implantable Venous Access Device (TIVAD) implantation. 8Fr single lumen catheter with Groshong non-return Valve (Bard Access Systems, Inc. USA) was inserted through right internal jugular vein, under fluoroscopic guidance. The catheter was tunneled subcutaneously and brought towards infraclavicular pocket, cut at appropriate length and connected to port and locked. Port was sutured in floor of pocket. Free flow of blood aspirated, flushed with heparinized saline. There was no kink observed in entire length of catheter under fluoroscopy. Skin over infraclavicular pocket was sutured. Long term catheter care and associated risks were explained to patient and relatives. Patient continued to receive total parenteral nutrition as well as other supportive therapy though TIVAD for next 6 weeks, till his demise. Conclusion: TIVADs are standard of care for long term venous access solutions in cancer patients requiring chemotherapy. In this case, we extended its use for providing parenteral nutrition and other supportive therapy. TIVADs can be implanted in advanced cancer patients for providing venous access solution required for various palliative treatments and medications. This will help in improving quality of life and satisfaction amongst terminally ill cancer patients.

Keywords: parenteral nutrition, totally implantable venous access device, long term venous access, interventions in anesthesiology

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Anushaa A.

Abstract:

In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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Authors: Hossein Miri, Zhou YongQi, Chan Bormei-Suy

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The development of advanced technologies and innovative solutions has opened up exciting new possibilities for revolutionizing healthcare systems. One such emerging concept is the use of virtual and holographic health information platforms that aim to provide interactive and personalized medical information to users. This paper provides a review of notable virtual and holographic health information platforms. It begins by highlighting the need for information visualization and 3D representation in healthcare. It then proceeds to provide background knowledge on information visualization and historical developments in 3D visualization technology. Additional domain knowledge concerning holography, holographic computing, and mixed reality is then introduced, followed by highlighting some of their common applications and use cases. After setting the scene and defining the context, the need and importance of virtual and holographic visualization in medicine are discussed. Subsequently, some of the current research areas and applications of digital holography and holographic technology are explored, alongside the importance and role of virtual and holographic visualization in genetics and genomics. An analysis of the key principles and concepts underlying virtual and holographic health information systems is presented, as well as their potential implications for healthcare are pointed out. The paper concludes by examining the most notable existing mixed-reality applications and systems that help doctors visualize diagnostic and genetic data and assist in patient education and communication. This paper is intended to be a valuable resource for researchers, developers, and healthcare professionals who are interested in the use of virtual and holographic technologies to improve healthcare.

Keywords: virtual, holographic, health information platform, personalized interactive medical information

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Authors: Ga-Young Lee, Hyun-Man Kim

Abstract:

The modulation of the cell-cell junction is critical in epithelial-mesenchymal transition during tumorigenesis. As RhoA activity is known to be up-regulated to dissociate cell-cell junction by contracting acto-myosin complex in various cancer cells, the present study investigated if RhoA activity was also associated with the disruption of the cell-cell junction of oral cancer cells. We studied SCC-25 cells which are established from oral squamous cell carcinoma if their E-cadherin junction (ECJ) was under control of RhoA. Interestingly, development of ECJ of SCC-25 cells depended on the amount of fibronectin (FN) coated on the culture dishes. Seeded cells promptly aggregated to develop ECJ on the substrates coated with a low amount of FN, whereas they were retarded in the development of ECJ on the substrates coated with a high amount of FN. However, it was an unexpected finding that total RhoA activity was lower in the dissociated cells on the substrates of high FN than in the aggregated cells on the substrates of low FN. Treating the dissociated cells on the substrates of high FN with LPA, a RhoA activator, promoted the development to ECJ. In contrast, treating the aggregated cells on the substrates of low FN with Clostridium botulinum C3, a toxin decreasing RhoA activity, dissociated cells concomitant with the disruption of ECJ. Genetical knockdown of RhoA expression by transfecting RhoA siRNA also down-regulated the development of ECJ in SCC-25 cells. Furthermore, PMA, an activator of protein kinase C (PKC), down-regulated the development of ECJ junction of SCC-25 cells on the substrates coated with low FN. In contrast, GO6976, a PKC inhibitor, up-regulated the development of ECJ of SCC-25 cells with the activation of RhoA on the substrates coated with high FN. In conclusion, in the present study, we demonstrated unexpected results that the activation of RhoA promotes the development of ECJ, whereas the inhibition of RhoA retards the development of ECJ in SCC-25 cells.

Keywords: E-cadherin junction, oral squamous cell carcinoma, PKC, RhoA, SCC-25

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Authors: Magdalena Chrabąszcz, Teresa Wolniewicz, Cezary Maciejewski, Joanna Czuwara

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BACKGROUND: Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin. Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer– related mortality and morbidity. Dermoscopy is a noninvasive technique that consists of viewing pigmented skin lesions through a hand-held lens. This simple procedure increases melanoma diagnostic accuracy by up to 35%. Dermoscopy is currently the standard for clinical differential diagnosis of cutaneous melanoma and for qualifying lesion for the excision biopsy. Like any clinical tool, training is required for effective use. The introduction of small and handy dermoscopes contributed significantly to the switch of dermatoscopy toward a first-level useful tool. Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. AIM: The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard fourth year medical curriculum improves the ability of medical students to distinguish between benign and malignant lesions and assess acceptability and satisfaction with the intervention. METHODS: We performed a prospective study in 2 cohorts of fourth-year medical students at Medical University of Warsaw. Groups having dermatology course, were randomly assigned to:  cohort A: with limited access to dermatoscopy from their teacher only – 1 dermatoscope for 15 people  Cohort B: with a full access to use dermatoscopy during their clinical classes:1 dermatoscope for 4 people available constantly plus 15-minute dermoscopy tutorial. Students in both study arms got an image-based test of 10 lesions to assess ability to differentiate benign from malignant lesions and postintervention survey collecting minimal background information, attitudes about the skin cancer examination and course satisfaction. RESULTS: The cohort B had higher scores than the cohort A in recognition of nonmelanocytic (P < 0.05) and melanocytic (P <0.05) lesions. Medical students who have a possibility to use dermatoscope by themselves have also a higher satisfaction rates after the dermatology course than the group with limited access to this diagnostic tool. Moreover according to our results they were more motivated to learn dermatoscopy and use it in their future everyday clinical practice. LIMITATIONS: There were limited participants. Further study of the application on clinical practice is still needed. CONCLUSION: Although the use of dermatoscope in dermatology as a specialty is widely accepted, sufficiently validated clinical tools for the examination of potentially malignant skin lesions are lacking in general practice. Introducing medical students to dermoscopy in their fourth year curricula of medical school may improve their ability to differentiate benign from malignant lesions. It can can also encourage students to use dermatoscopy in their future practice which can significantly improve early recognition of malignant lesions and thus decrease melanoma mortality.

Keywords: dermatoscopy, early detection of melanoma, medical education, skin cancer

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Authors: Devadrita Dey Sarkar

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Regardless of the many technologic advances in the past decade, increased training and experience, and the obvious benefits of uniform standards, the false-negative rate in screening mammography remains unacceptably high .A computer aided neural network classification of regions of suspicion (ROS) on digitized mammograms is presented in this abstract which employs features extracted by a new technique based on independent component analysis. CAD is a concept established by taking into account equally the roles of physicians and computers, whereas automated computer diagnosis is a concept based on computer algorithms only. With CAD, the performance by computers does not have to be comparable to or better than that by physicians, but needs to be complementary to that by physicians. In fact, a large number of CAD systems have been employed for assisting physicians in the early detection of breast cancers on mammograms. A CAD scheme that makes use of lateral breast images has the potential to improve the overall performance in the detection of breast lumps. Because breast lumps can be detected reliably by computer on lateral breast mammographs, radiologists’ accuracy in the detection of breast lumps would be improved by the use of CAD, and thus early diagnosis of breast cancer would become possible. In the future, many CAD schemes could be assembled as packages and implemented as a part of PACS. For example, the package for breast CAD may include the computerized detection of breast nodules, as well as the computerized classification of benign and malignant nodules. In order to assist in the differential diagnosis, it would be possible to search for and retrieve images (or lesions) with these CAD systems, which would be reliable and useful method for quantifying the similarity of a pair of images for visual comparison by radiologists.

Keywords: CAD(computer-aided design), lesions, neural network, ROS(region of suspicion)

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Authors: Adriana C. Panayi, Riaz A. Agha, Brady A. Sieber, Dennis P. Orgill

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Background: Increased rates of both breast cancer and obesity have resulted in more women seeking breast reconstruction. These women may be at increased risk for perioperative complications. A systematic review was conducted to assess the outcomes in obese women who have undergone breast reconstruction following mastectomy. Methods: Cochrane, PUBMED and EMBASE electronic databases were screened and data was extracted from included studies. The clinical outcomes assessed were surgical complications, medical complications, length of postoperative hospital stay, reoperation rate and patient satisfaction. Results: 33 studies met the inclusion criteria for the review and 29 provided enough data to be included in the meta-analysis (71368 patients, 20061 of which were obese). Obese women were 2.3 times more likely to experience surgical complications (95 percent CI 2.19 to 2.39; P < 0.00001), 2.8 times more likely to have medical complications (95 percent CI 2.41 to 3.26; P < 0.00001) and had a 1.9 times higher risk of reoperation (95 percent CI 1.75 to 2.07; P < 0.00001). The most common complication, wound dehiscence, was 2.5 times more likely in obese women (95 percent CI 1.80 to 3.52; P < 0.00001). Sensitivity analysis confirmed that obese women were more likely to experience surgical complications (RR 2.36, 95% CI 2.22–2.52; P < 0.00001). Conclusions: This study provides evidence that obesity increases the risk of complications in both implant and autologous reconstruction. Additional prospective and observational studies are needed to determine if weight reduction prior to reconstruction reduces the perioperative risks associated with obesity.

Keywords: autologous reconstruction, breast cancer, breast reconstruction, literature review, obesity, oncology, prosthetic reconstruction

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Authors: Sujeet Poudyal

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Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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Authors: Ravi Kiran Pothamsetty, Radha Rani Ghosh, Baby Paul Thaliath

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Radiation therapy has undergone many advancements and evloved from 2D to 3D. Recently, with rapid pace of drug discoveries, cutting edge technology, and clinical trials has made innovative advancements in computer technology and treatment planning and upgraded to intensity modulated radiotherapy (IMRT) which delivers in homogenous dose to tumor and normal tissues. The present study was a hospital-based experience comparing two different conformal radiotherapy techniques for brain tumors. This analytical study design has been conducted at Regional Cancer Centre, India from January 2014 to January 2015. Ten patients have been selected after inclusion and exclusion criteria. All the patients were treated on Artiste Siemens Linac Accelerator. The tolerance level for maximum dose was 6.0 Gyfor lenses and 54.0 Gy for brain stem, optic chiasm and optical nerves as per RTOG criteria. Mean and standard deviation values of PTV98%, PTV 95% and PTV 2% in IMRT were 93.16±2.9, 95.01±3.4 and 103.1±1.1 respectively; for 3DCRT were 91.4±4.7, 94.17±2.6 and 102.7±0.39 respectively. PTV max dose (%) in IMRT and 3D-CRT were 104.7±0.96 and 103.9±1.0 respectively. Maximum dose to the tumor can be delivered with IMRT with acceptable toxicity limits. Variables such as expertise, location of tumor, patient condition, and TPS influence the outcome of the treatment.

Keywords: brain tumors, intensity modulated radiotherapy (IMRT), three dimensional conformal radiotherapy (3D-CRT), radiation therapy oncology group (RTOG)

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