CENP-B specific anti-centromere autoantibodies heralding small-cell lung cancer. A case study and review of the literature

We report on a small-cell lung cancer case that was heralded by the presence of CENP-B specific anti-centromere autoantibodies (ACA) detected well before the diagnosis of cancer. The patient received chemotherapy plus radiotherapy, which resulted in complete remission of the tumor. Serum ACA levels were zeroed at the time of radiological documentation of tumor response and remained undetected at serial follow-up assessments until they rose again along with documentation of tumor recurrence which occurred 12 months later. We review in brief published research and discuss anti-centromere autoantibodies as potential biomarkers in small-cell lung cancer, a highly proliferative tumor which lacks sensitive serum markers.     

The kisspeptin (KiSS-1)/GPR54 system in cancer biology

Kisspeptin (KiSS-1) gene, initially described as a melanoma metastasis suppressor gene, encodes a number of peptides (kp-54, kp-14, kp-13, kp-10), which are endogenous ligands to a G protein-coupled receptor, referred as hOT7T175 or AXOR12 or GPR54. So far intensive investigation has provided substantiate evidence supporting the role of KiSS-1/GPR54 system in cancer biology as well as in the regulation of the reproductive function and trophoblast invasion. The precise mechanism by which KiSS-1/GPR54 system is affecting cancer cell growth and metastasis includes complex endocrine, paracrine and autocrine actions. Nevertheless, the detail mechanism of such actions is still under intensive investigation. Herein we review the evidence which support the role of KiSS-1/GPR54 system in cancer biology.     

Cytokine concentrations during the first days of life

OBJECTIVE: To evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period. SUBJECTS AND METHODS: Forty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults. RESULTS: IL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-gamma concentrations increased significantly from umbilical cord to 5th day of life. CONCLUSION: Our findings indicate a dysregulation among IL-2, IL-4 and IFN-gamma concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-gamma that seems to be ameliorated in the end of the 1st week of life.     

Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules

Morpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules. It is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes. The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active-site inhibitors whereas it bestows selective affinity for a wide range of receptors. A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug-like properties and improved pharamacokinetics. In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.     

Phase I/II Trial of External Irradiation plus Medium-Dose Brachytherapy Given Concurrently to Liposomal Doxorubicin and Cisplatin for Advanced Uterine Cervix Carcinoma

BACKGROUND AND PURPOSE: Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. PATIENTS AND METHODS: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week. RESULTS: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). CONCLUSION: Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.     

Trust me,I’m a researcher!: The role of trust in biomedical research

In biomedical research lack of trust is seen as a great threat that can severely jeopardise the whole biomedical research enterprise. Practices, such as informed consent, and also the administrative and regulatory oversight of research in the form of research ethics committees and Institutional Review Boards, are established to ensure the protection of future research subjects and, at the same time, restore public trust in biomedical research. Empirical research also testifies to the role of trust as one of the decisive factors in research participation and lack of trust as a barrier for consenting to research. However, what is often missing is a clear definition of trust. This paper seeks to address this gap. It starts with a conceptual analysis of the term trust. It compares trust with two other related terms, those of reliance and trustworthiness, and offers a defence of Baier’s attribute of ‘good will’ a basic characteristic of trust. It, then, proceeds to consider trust in the context of biomedical research by examining two questions: First, is trust necessary in biomedical research?; and second, do increases in regulatory oversight of biomedical research also increase trust in the field? This paper argues that regulatory oversight is important for increasing reliance in biomedical research, but it does not improve trust, which remains important for biomedical research. It finishes by pointing at professional integrity as a way of promoting trust and trustworthiness in this field.