Large-duct pattern invasive adenocarcinoma of the pancreas–a variant mimicking pancreatic cystic neoplasms: A minireview

Pancreatic cancer currently has no subtypes that inform clinical decisions; hence, there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics. Nonetheless, accumulating studies to date have revealed the large-duct type variant, a unique subtype of pancreatic ductal adenocarcinoma (PDA) with cystic features. This subtype often radiographically mimics intraductal papillary mucinous neoplasms (IPMNs) and involves multiple small cysts occasionally associated with solid masses. The “bunch-of-grapes” sign, an imaging characteristic of IPMNs, is absent in large-duct PDA. Large-duct PDA defines the mucin profile, and genetic alterations are useful in distinguishing large-duct PDA from IPMNs. Histologically, neoplastic ducts measure over 0.5 mm, forming large ductal elements. Similar to classic PDAs, this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions, and KRAS mutations in codon 12 are nearly ubiquitous. Despite such morphological similarities with IPMNs, the prognosis of large-duct PDA is equivalent to that of classic PDA. Differential diagnosis is therefore essential.     

Correlation between haemoglobin level and type of erythropoiesis-stimulating agent at initiation of haemodialysis

International Journal of Clinical Pharmacy - Background Renal anaemia worsens because of the uraemic status immediately before the initiation of haemodialysis. The haemoglobin level in patients...     

Conformational investigation of peptides using solid‐state NMR spectroscopy—A study of polymorphism of β‐turn peptides containing diprolines

The construction of complex protein folds relies on the precise conversion of a linear polypeptide chain into a compact 3‐dimensional structure. In this context, study of isolated secondary structural modules containing short stretches of amino acids assumes significance. Additionally, peptides, both natural and synthetic, play a major role as potential drugs. With a view to understand the local conformations adopted by peptides in the solid state, we propose a multinuclear NMR approach utilizing spectra of nuclei in their natural isotopic abundance. Various solid‐state NMR experiments have been utilized for assignment of the spectra. Additionally, the gauge‐including projector augmented‐wave (GIPAW) calculations were used to confirm the assignments. Particularly, the utility of the double‐quantum–single‐quantum correlation experiments is highlighted for the purpose of assignment and for inferring the conformation across the peptide bond. The methodology is illustrated for the case of designed peptides containing diproline residues occurring at the β‐turns for identifying their cis‐trans conformational polymorphism. The proposed method promises to be of use in the study of conformations of small‐ to medium‐sized peptides such as antimicrobial peptides and in the study of polymorphism leading to applications in drug development protocols.     

Generation of a large number of functional dendritic cells from human monocytes expanded by forced expression of cMYC plus BMI1

Anticancer vaccination therapies with monocyte-derived dendritic cells (DC) are widely conducted. A large number of primary monocytes (approximately 10⁸ cells) are needed to generate the number of DC required to achieve an effect upon vaccination, and monocytes are usually purified from peripheral blood mononuclear cells obtained by apheresis procedure, which is somehow invasive for cancer patients. As a means to facilitate the generation of DC for therapeutic use, we herein report a method to amplify human monocytes. We found that lentivirus-mediated transduction of cMYC along with BMI1 induced proliferation of CD14⁺ monocytes derived from 9 out of 12 blood donors, and we named the monocyte-derived proliferating cells CD14-ML. Their proliferation continued for 3–5 weeks in the presence of M-CSF and GM-CSF, resulting in 20–1000-fold amplification. Importantly, the expanded CD14-ML differentiated into fully functional DC (CD14-ML-DC) upon the addition of IL-4 to the culture. We successfully stimulated autologous CD8⁺ T cells with CD14-ML-DC pulsed with cytomegalovirus peptide or MART-1 peptide to generate antigen-specific CTL lines. This is the first report describing the method for in vitro expansion of human peripheral blood monocytes.     

Prediction of Treatment Efficacy and Telaprevir-Resistant Variants after Triple Therapy in Patients Infected with Hepatitis C Virus Genotype 1

It is often difficult to predict the response to telaprevir-pegylated interferon (PEG-IFN)-ribavirin triple therapy and the appearance of telaprevir-resistant variants. The present study determined the predictive factors of a sustained virological response (SVR) to 12- or 24-week triple therapy (T12PR12 or T12PR24, respectively) in 194 Japanese patients infected with hepatitis C virus genotype 1b (HCV-1b). The study also evaluated whether ultradeep sequencing technology can predict at baseline the emergence of resistant variants after the start of therapy. Analysis of the data of the entire group indicated that an SVR was achieved in 78% of the patients. Multivariate analysis identified IL28B rs8099917 (genotype TT), the substitution of amino acid (aa) 70 (Arg70), response to prior treatment (naive or relapse), PEG-IFN dose (≥1.3 μg/kg of body weight), and treatment regimen (T12PR24) as significant determinants of SVR. Among patients of the T12PR24 group, 92% with genotype TT achieved an SVR, irrespective of a substitution at aa 70. In patients with the non-TT genotype, an SVR was achieved in 76% of those with Arg70, while only 14% of patients with the non-TT genotype, Gln70(His70), and nonresponse to ribavirin combination therapy achieved an SVR. Ultradeep sequencing was conducted for 17 patients who did not achieve an SVR to determine the emergence of resistant variants during therapy. De novo resistant variants were detected in 16 of 17 patients (94%), regardless of the variant frequencies detected at baseline. In conclusion, the results indicate that the response to triple therapy can be predicted by the combination of host, viral, and treatment factors and that it is difficult to predict at baseline the telaprevir-resistant variants that emerge during triple therapy, even with the use of ultradeep sequencing.     

Two cases of atypical femoral fracture in cancer patients administered with bone-modifying agents

Objective: We report two cases of atypical femoral fracture (AFF) in patients with cancer.Patients: Two patients, a 53-year-old woman with breast cancer and a 77-year-old man with prostate cancer, could not walk after being injured in a fall. They used bone-modifying agents (BMA) for the prevention of bone metastasis for three and four years, respectively.Results: Intramedullary nails were placed to fix the femoral fractures in each patient. Neither of them had pathological metastatic femoral fractures based on fracture site specimens; however, severe suppression of bone turnover at the fracture site was suspected. Both patients could ambulate with a T-cane and were free of hip pain after surgery. Radiographs showed no callus formation at the fracture site.Conclusion: Based on the two cases of AFF in patients with cancer related to BMA use, we should consider that the incidence of AFF may be associated with long-term BMA use.