Surgical Ophthalmic Oncology

Designed as an easy-to-use, practical guide to tumors of the eye, lids, and orbit, this Open Access book comprehensively addresses surgical treatment and management of diseases related to ophthalmic oncology. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is an ideal reference for general ophthalmologists, surgeons, fellows and trainees around the world who encounter these diseases in the care of their patients. Notably, this book includes considerations for those ophthalmologists offering subspecialty care in environments with limited access to advanced technology and instrumentation. Individual chapters address diagnostic indications, pre-operative and post-operative concerns, and provide detailed explanations of surgical techniques required to manage various eye cancer ailments with help of ample illustrations. High-quality videos included throughout the book provide readers with the opportunity to review surgical steps in real-time as a learning tool. Chapters thoroughly cover tumors of eyelid, cornea and conjunctiva, orbit as well as intraocular tumors, while later chapters discuss ophthalmic radiation therapy. The book concludes with a section on ophthalmic pathology which details essential guidelines on relevant aspects from specimen collection and transport, to interpretation of the pathology report. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is a unique and necessary valuable resource for ophthalmologists, trainees, and related medical professionals working in underserved areas in providing quality care for patients suffering from ocular cancers. ; Open Access text that discusses Preferred Practice Guidelines for common surgeries performed on tumors of the eye and adnexa Written for general ophthalmologists providing oncology care and specialists practicing in areas with limited access to advanced technology and instrumentation Includes chapters on eyelid tumors, conjunctival and corneal tumors, intraocular tumors, brachytherapy, and ocular pathology Each chapter includes extensive color pictures and relevant video to assist the clinician in the various surgical procedures discusse

Colorectal Cancer

Colorectal cancer is one of the commonest cancers affecting individuals across the world. An improvement in survival has been attributed to multidisciplinary management, better diagnostics, improved surgical options for the primary and metastatic disease and advances in adjuvant therapy. In this book, international experts share their experience and knowledge on these different aspects in the management of colorectal cancer. An in depth analysis of screening for colorectal cancer, detailed evaluation of diagnostic modalities in staging colorectal cancer, recent advances in adjuvant therapy and principles and trends in the surgical management of colorectal cancer is provided. This will certainly prove to be an interesting and informative read for any clinician involved in the management of patients with colorectal cancer

Unsupervised multiple kernel learning approaches for integrating molecular cancer patient data

Cancer is the second leading cause of death worldwide. A characteristic of this disease is its complexity leading to a wide variety of genetic and molecular aberrations in the tumors. This heterogeneity necessitates personalized therapies for the patients. However, currently defined cancer subtypes used in clinical practice for treatment decision-making are based on relatively few selected markers and thus provide only a coarse classifcation of tumors. The increased availability in multi-omics data measured for cancer patients now offers the possibility of defining more informed cancer subtypes. Such a more fine-grained characterization of cancer subtypes harbors the potential of substantially expanding treatment options in personalized cancer therapy. In this thesis, we identify comprehensive cancer subtypes using multidimensional data. For this purpose, we apply and extend unsupervised multiple kernel learning methods. Three challenges of unsupervised multiple kernel learning are addressed: robustness, applicability, and interpretability. First, we show that regularization of the multiple kernel graph embedding framework, which enables the implementation of dimensionality reduction techniques, can increase the stability of the resulting patient subgroups. This improvement is especially beneficial for data sets with a small number of samples. Second, we adapt the objective function of kernel principal component analysis to enable the application of multiple kernel learning in combination with this widely used dimensionality reduction technique. Third, we improve the interpretability of kernel learning procedures by performing feature clustering prior to integrating the data via multiple kernel learning. On the basis of these clusters, we derive a score indicating the impact of a feature cluster on a patient cluster, thereby facilitating further analysis of the cluster-specific biological properties. All three procedures are successfully tested on real-world cancer data. Comparing our newly derived methodologies to established methods provides evidence that our work offers novel and beneficial ways of identifying patient subgroups and gaining insights into medically relevant characteristics of cancer subtypes.Krebs ist eine der häufigsten Todesursachen weltweit. Krebs ist gekennzeichnet durch seine Komplexität, die zu vielen verschiedenen genetischen und molekularen Aberrationen im Tumor führt. Die Unterschiede zwischen Tumoren erfordern personalisierte Therapien für die einzelnen Patienten. Die Krebssubtypen, die derzeit zur Behandlungsplanung in der klinischen Praxis verwendet werden, basieren auf relativ wenigen, genetischen oder molekularen Markern und können daher nur eine grobe Unterteilung der Tumoren liefern. Die zunehmende Verfügbarkeit von Multi-Omics-Daten für Krebspatienten ermöglicht die Neudefinition von fundierteren Krebssubtypen, die wiederum zu spezifischeren Behandlungen für Krebspatienten führen könnten. In dieser Dissertation identifizieren wir neue, potentielle Krebssubtypen basierend auf Multi-Omics-Daten. Hierfür verwenden wir unüberwachtes Multiple Kernel Learning, welches in der Lage ist mehrere Datentypen miteinander zu kombinieren. Drei Herausforderungen des unüberwachten Multiple Kernel Learnings werden adressiert: Robustheit, Anwendbarkeit und Interpretierbarkeit. Zunächst zeigen wir, dass die zusätzliche Regularisierung des Multiple Kernel Learning Frameworks zur Implementierung verschiedener Dimensionsreduktionstechniken die Stabilität der identifizierten Patientengruppen erhöht. Diese Robustheit ist besonders vorteilhaft für Datensätze mit einer geringen Anzahl von Proben. Zweitens passen wir die Zielfunktion der kernbasierten Hauptkomponentenanalyse an, um eine integrative Version dieser weit verbreiteten Dimensionsreduktionstechnik zu ermöglichen. Drittens verbessern wir die Interpretierbarkeit von kernbasierten Lernprozeduren, indem wir verwendete Merkmale in homogene Gruppen unterteilen bevor wir die Daten integrieren. Mit Hilfe dieser Gruppen definieren wir eine Bewertungsfunktion, die die weitere Auswertung der biologischen Eigenschaften von Patientengruppen erleichtert. Alle drei Verfahren werden an realen Krebsdaten getestet. Den Vergleich unserer Methodik mit etablierten Methoden weist nach, dass unsere Arbeit neue und nützliche Möglichkeiten bietet, um integrative Patientengruppen zu identifizieren und Einblicke in medizinisch relevante Eigenschaften von Krebssubtypen zu erhalten

Surgical Ophthalmic Oncology

Designed as an easy-to-use, practical guide to tumors of the eye, lids, and orbit, this Open Access book comprehensively addresses surgical treatment and management of diseases related to ophthalmic oncology. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is an ideal reference for general ophthalmologists, surgeons, fellows and trainees around the world who encounter these diseases in the care of their patients. Notably, this book includes considerations for those ophthalmologists offering subspecialty care in environments with limited access to advanced technology and instrumentation. Individual chapters address diagnostic indications, pre-operative and post-operative concerns, and provide detailed explanations of surgical techniques required to manage various eye cancer ailments with help of ample illustrations. High-quality videos included throughout the book provide readers with the opportunity to review surgical steps in real-time as a learning tool. Chapters thoroughly cover tumors of eyelid, cornea and conjunctiva, orbit as well as intraocular tumors, while later chapters discuss ophthalmic radiation therapy. The book concludes with a section on ophthalmic pathology which details essential guidelines on relevant aspects from specimen collection and transport, to interpretation of the pathology report. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is a unique and necessary valuable resource for ophthalmologists, trainees, and related medical professionals working in underserved areas in providing quality care for patients suffering from ocular cancers. ; Open Access text that discusses Preferred Practice Guidelines for common surgeries performed on tumors of the eye and adnexa Written for general ophthalmologists providing oncology care and specialists practicing in areas with limited access to advanced technology and instrumentation Includes chapters on eyelid tumors, conjunctival and corneal tumors, intraocular tumors, brachytherapy, and ocular pathology Each chapter includes extensive color pictures and relevant video to assist the clinician in the various surgical procedures discusse

INHALABLE NANOCOMPOSITES AND ANTICANCER AGENTS FOR CANCER THERAPY

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and higher quality of life for lung cancer patients receiving such harsh chemotherapy regimens. In this work, a novel lung cancer treatment modality is presented wherein ACAs are incorporated into inhalable dry powder composites for targeted delivery to the pulmonary tract. Additionally, nanoparticles were added to inhalable composites to increase the therapeutic potential of these unique materials. A variety of dry powder composites were formulated via spray drying and the physicochemical properties of the resulting systems were characterized. Additionally, the performance of the cargo incorporated into these composites was evaluated in order to insure the activity of the components after release from the inhalable dry powders. The aerodynamic performance of the dry powder systems was evaluated with the Next Generation Impactor® to determine if these materials were suitable for inhalation purposes. Iron oxide (Fe3O4) magnetic nanoparticles were synthesized and incorporated into dry powders to examine the feasibility of administering these materials to the lungs for remotely actuated hyperthermia. Remote heating studies were performed on the nanoparticles released from these composites using a custom Taylor Winfield® alternating magnetic field source, and in vitro hyperthermia studies were performed using advanced multicellular spheroid cell culture models. These studies elicited the effectiveness of these systems on physiologically relevant models. In addition to the iron oxide composites, dry powders were formulated with two common ACAs, cisplatin and erlotinib, for inhalable chemotherapy. The activity of the drugs released from these composites was evaluated on the human pulmonary lung cancer cell lines A549 and H358 and compared with the free form of the drugs in order to evaluate the effectiveness of these therapies. Finally, responsive hydrogel nanoparticles (HNPs) that contain the ability to respond to environmental changes in pH were synthesized and evaluated as responsive drug carriers. The response of these particles to pH was evaluated and their stability was examined before and after inclusion into dry powder composites. Overall, inhalable dry powder nanocomposites are promising materials for innovative lung cancer treatment modalities and have the potential to provide a safer and more effective option for addressing this devastating disease

Alternations of microRNAs, the microbiome, and gut-host interactions in gastrointestinal diseases

Over the past few decades, an ageing population combined with a shift towards a Western lifestyle has predisposed many individuals towards inter-connected gastrointestinal (GI) diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), gastric cancer (GC) and Clostridioides difficile (C. difficile) infection (CDI). anti-TNF-α treatment for IBD patients has a high unresponsive rate, by using bioinformatics approaches, I identified neutrophil chemotaxis may contribute to the treatment resistance and IL13RA2 is the best predictor to identify treatment unresponsive patients. On the other hand, in the intestinal tract, colonocytes consistently exfoliate and shed into the lumen, affecting gut microbiota composition. These molecular/microbial changes involved in disease pathogenesis can be detected in faeces. By using Taqman probe-based real-time polymerase chain reaction (RT qPCR) assay, several non-coding microRNAs (such as miR-18a, miR-20a, miR-221 and miR 135b) and gut microbes (including Fusobacterium nucleatum, Parvimonas micra, Gemella morbillorum, Peptostreptococcus anaerobius, Clostridium hathewayi and Lachnoclostrium sp.) are highly expressed/enriched in faeces in CRC individuals compared to control subjects. The use of a faecal immunological test (FIT) in combination with these biomarkers may improve the non-invasive CRC screening accuracy. Furthermore, Epstein-Barr virus (EBV) is an oncogenic virus and EBV-driven GC accounts for roughly 10% of total GC cases. GC cells infected with EBV alter the molecular aspect at whole-genome, transcriptome, and epigenome levels. For instance, AKT2 activated by mutation in EBV-positive GC cells affecting downstream MAPK and focal adhesion signalling pathways; AKT2 mutation associates with poor patient survival in EBV-positive GC. Furthermore, once patients have received GI treatments, it may suppress/interfere with the patients’ immune system, disrupt the gut flora homeostasis and trigger CDI. Faecal microbiota transplantation (FMT) has been demonstrated as an effective and alternative treatment strategy for CDI patients. However, it is still in clinical trials due to safety concerns. My study revealed that serum miRNAs such as miR-23a-3p, miR-150-5p, miR-26b-5p and miR-28-5p could be used to monitor FMT treatment in CDI patients, and these markers inversely correlate with IL-12B, IL-18, FGF21 and TNFSRF9 at serum protein and mRNA levels, respectively. Furthermore, miR-23a and miR-150 showed cytoprotective effects against C. difficile Toxin B (TcdB)