Pancreatic ductal adenocarcinoma (PDAC), with a mortality rate of 94% and a 5-year-survival rate of only 8%, is one of the deadliest cancer entities worldwide, and early diagnostic methods as well as effective therapies are urgently needed.

This review summarizes current clinical procedure and recent developments of oncological therapy in the palliative setting of metastatic PDAC. It further gives examples of successful, as well as failed, targeted therapy approaches and finally discusses promising ongoing research into the decade-old question of the „undruggability” of KRAS.

Bench-driven concepts change the clinical landscape from „one size fits all” towards precision medicine. With growing insight into the molecular mechanisms of pancreatic cancer the era of targeted therapy in PDAC is gaining a new momentum.

Bench-driven concepts change the clinical landscape from „one size fits all” towards precision medicine. With growing insight into the molecular mechanisms of pancreatic cancer the era of targeted therapy in PDAC is gaining a new momentum.

Gastric cancer (GC) is one of the most lethal cancers worldwide. Although GC was historically considered a single entity within the organ of origin, nowadays it is acknowledged that GC represents a heterogeneous disease. Nevertheless, in this field there is still a lack of biomarkers able to guide the choice of the best treatment options for each patient. This review aims to summarize the prognostic and predictive biomarkers evaluated in GC and their role as a guide for treatment for precision medicine.

Human epidermal growth factor receptor 2 overexpression represents the only predictive molecular biomarker validated in GC, while its prognostic role is still controversial. Microsatellite instability and Epstein-Barr virus status are promising for prediction of the response to immunotherapy. The role of other biomarkers (ctDNA, programmed death ligand 1 [PD-L1], and TMB), as well as the practical application of molecular classifications, requires further evaluation before use in clinical practice. 18-FDG-PET scan could be useful as a predictive tool in non-metastatic GC patients receiving a perioperative approach. Finally, the tumor microenvironment may have an evolving role in the future.

GC is a heterogeneous disease and targeted approaches are needed. The finding of prognostic and predictive factors is a hot topic in the field of GC personalized medicine.

GC is a heterogeneous disease and targeted approaches are needed. The finding of prognostic and predictive factors is a hot topic in the field of GC personalized medicine.

Clinical trials have proven a survival benefit from applying local therapies for oligometastatic cancers of various origin.

Today, the definition of oligometa-static disease is based on limited lesion numbers and organ systems involved. Treatment guidelines by the European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO) and several other groups suggest a threshold of up to 5 tumours. Established biological markers indicating the aggressiveness of a given tumour (and therefore suggesting local treatment only or the addition of or complete switch to systemic therapies) are missing, except for disease-free survival, the only recommended parameter for patient selection beyond lesion count.

The following article discusses clinical implications as well as local techniques established for the treatment of oligometastatic disease.

The following article discusses clinical implications as well as local techniques established for the treatment of oligometastatic disease.

Surgery is the standard treatment for primary tumors and metastases. Due to improvements in surgical outcomes as well as the efficacy of systemic treatments, the role of surgery has changed in recent years.

Liver surgery has become safe and efficient, with resectability being increased by multimodality concepts as well as staged liver resections and orthotopic liver transplantation. These concepts may be applied to primary liver tumors but also to selected patients with liver metastases from various diseases. In addition, even debulking surgery may be indicated for selected patients with endocrine metastases. While patient selection for liver resections was limited to clinical parameters in the past, histological and molecular characteristics have become increasingly important. Moreover, the response to regional or systemic chemotherapy has been demonstrated to be strong for a beneficial course of the disease even in advanced diseases.

Due to the variety of available treatment options, optimal patient selection is crucial. Besides liver surgery, staged concepts as well as liver transplantation are curative tools for many patients.

Due to the variety of available treatment options, optimal patient selection is crucial. Besides liver surgery, staged concepts as well as liver transplantation are curative tools for many patients.Being a model for endangered wild felids, cryopreservation protocols for domestic cat oocytes are under continuous development. Immature vitrified oocytes (VOs) are a valuable resource for fertility preservation programs, but they often degenerate after warming and their in vitro development is poor. Since the exact mechanisms are not clear, this study assessed whether vitrification might trigger two apoptotic markers (DNA fragmentation and caspase activity, Experiment I) and the effects of a chemical inhibitor (i.e., the pan-caspase inhibitor Z-VAD-FMK) on the same markers (Experiment II) and on VOs in vitro development (Experiment III). The overarching aim was to check whether apoptosis inhibition might be a strategy to improve cat oocytes cryotolerance. In Experiment I, vitrification induced DNA fragmentation and increased caspase activity in VOs incubated for 24 h after warming (DNA fragmentation 59.38%; caspase activity 414.6 ± 326.8) compared to a fresh control (9.68%; 199.6 ± 178.3; p = 0.02). In Experiment II, the addition of Z-VAD-FMK to vitrification-warming and incubation media decreased DNA fragmentation and caspase activity (8.82%; 243.7 ± 106.9) compared to control (untreated) VOs (69.44%; 434.5 ± 248.3; p less then 0.001). In Experiment III, Z-VAD-FMK brought maturation rates of treated VOs close to those of fresh oocytes (53.13 and 65.38%, respectively, p = 0.057), but there were no differences in VOs embryo development (cleavage rates; Z-VAD-FMK-treated VOs 34.38%; control VOs 31.78%; p = 0.69). In summary, vitrification increased apoptotic markers in cat VOs, and while Z-VAD-FMK was able to hinder DNA damage and caspase activity, its addition was not determinant for embryo development. To make the best use of VOs, other oocyte in vitro maturation and embryo culture strategies, such as the addition of other inhibitors or their prolonged use, should be investigated.The identification of cross-reactive monoclonal antibodies (mAbs) that recognize orthologous leukocyte differentiation molecules (LDM) in buffaloes has overcome a major impediment limiting research on the immune response to pathogens and development of vaccines. As reported, two pilot trials were conducted to accomplish two objectives (1) demonstrate that multiparameter flow cytometry can be conducted equally well in buffalo with mAbs directly and indirectly labeled with fluorochromes in research and (2) flow cytometry can be used to compare and extend studies on diseases of economic importance to buffalo using bovine viral diarrhea virus (BVDV) as a model pathogen. Pregnant buffalo cows were infected with BVDV-1 at 81 (trial 1) and 203 (trial 2) days post artificial insemination and flow cytometric evaluations were performed at 0, 3, 4, and 14 days after infection (dpi). Fluorochrome conjugated mAbs were used in trial 1, and fluorochrome conjugated goat isotype specific anti-mouse antibodies were used to labtudies have demonstrated that it is possible to use multicolour multiparameter flow cytometry to study the immune response to pathogens affecting the health of buffalo.Objectives We aimed to determine the effect of intravenous morphine injection on the modified Frankel scores of dogs with thoracolumbar intervertebral disk extrusion (IVDE). Methods This was a prospective, blinded, randomized, and placebo-controlled study. We included dogs with a presumptive diagnosis of thoracolumbar IVDE that did not undergo analgesic, anti-inflammatory, or sedative treatment within the last 12 h. A neurological examination was performed and the deficits were graded using the modified Frankel score (MFS). Subsequently, each dog was randomly allocated to receive an intravenous injection of either morphine or placebo. After 30 min, the dogs were re-evaluated by the same veterinary officer who was blinded to the contents of the injections. Dogs were included in the study if IVDE was ultimately confirmed by surgery within one week of initial presentation. Results Among the 79 dogs initially enrolled, 62 dogs met the inclusion criteria. Among them, thirty-two dogs received intravenous morphine injections and there was no difference between the pre- and post-injection modified Frankel scores. Thirty dogs received an intravenous placebo injection. One dog had a worsening of the MFS by one grade in the post-injection examination. Clinical Significance In dogs with thoracolumbar intervertebral disk extrusion, an intravenous injection of morphine does not affect the modified Frankel score after 30 min compared with the pre-injection value. These findings support the use of an analgesic morphine dose if the neurological examination can be performed 30 min or later after the injection.Canine atopic dermatitis (CAD) has a hereditary basis that is modified by interactions with the environment, including diet. Differentially expressed genes in non-lesional skin, determined by RNA sequencing before and after a dietary intervention, were compared between dogs with naturally occurring CAD (n = 4) and healthy dogs (n = 4). The dogs were fed either a common commercial heat-processed high carbohydrate food (kibble diet) (n = 4), or a non-processed high fat food (raw meat-based diet) (n = 4). At the end of the diet intervention, 149 differentially expressed transcripts were found between the atopic and healthy dogs. The main canonical pathways altered by the dysregulation of these genes were angiopoietin signaling, epidermal growth factor signaling, activation of angiogenesis, and alterations in keratinocyte proliferation and lipid metabolism. On the other hand, 33 differently expressed transcripts were found between the two diet groups, of which 8 encode genes that are annotated in the current version of the dog genome immunoglobulin heavy constant mu (IGHM), immunoglobulin lambda-like polypeptide 5 (IGLL5), B-cell antigen receptor complex-associated protein beta chain (CD79B), polymeric immunoglobulin receptor (PIGR), cystathionine β-synthase (CBS), argininosuccinate synthase 1 (ASS1), secretory leukocyte peptidase inhibitor (SLPI), and mitochondrial ribosome recycling factor (MRRF). All genes were upregulated in the raw diet group. In conclusion the findings of this study suggest alterations in lipid and keratinocyte metabolism as well as angiogenesis in the skin of atopic dogs. Additionally, a possible enhancement of innate immunity and decrease in oxidative stress was seen in raw food fed dogs, which could have an important role in preventing hypersensitivities and disturbed immunity at young age.