Recent developments in the cleavage, functionalization, and conjugation of proteins and peptides at tyrosine residues.

Peptide and protein selective modification at tyrosine residues has become an exploding field of research as tyrosine constitutes a robust alternative to lysine and cysteine-targeted traditional peptide/protein modification protocols. This review offers a comprehensive summary of the latest advances in tyrosine-selective cleavage, functionalization, and conjugation of peptides and proteins from the past three years. This updated overview complements the extensive body of work on site-selective modification of peptides and proteins, which holds significant relevance across various disciplines, including chemical, biological, medical, and material sciences.

Synthesis and antiproliferative activity of C- and N-terminal analogues of culicinin D.

Culicinin D (1), a 10 amino acid peptaibol containing several unusual residues, has been shown to exhibit potent anticancer activity. Previous work in our group towards developing a structure-activity relationship (SAR) for this peptaibol has concentrated on replacement of the synthetically challenging AHMOD (3) and AMD (4) residues, resulting in the discovery of analogues with equivalent or better potency and simplified synthesis. The SAR of this peptaibol is extended in this work by investigating the effect of the N-terminal lipid tail and C-terminal amino alcohol, revealing the key contribution of each of these moieties on antiproliferative activity in a panel of breast and lung cancer cell lines.

Implementation strategies for depression and anxiety screening in a pediatric cystic fibrosis center: A quality improvement project.

BACKGROUND: Guidelines to integrate mental health screening (MHS) into Cystic fibrosis (CF) care has increased adoption across the United States and European CF Centers, however, there has been limited discussion on specific strategies for implementation. OBJECTIVE: Share key strategies that led to successful MHS implementation in one pediatric CF center and report implementation and screening outcomes. METHODS: Parent partners, mental health experts from the Department of Psychiatry, and the CF clinic team codesigned interventions to support three major stakeholders: (a) patients and families (b) clinic team, and (c) hospital system. The mental health coordinator approached patients (12 and older) to introduce MHS and administered screening and reviewed results using an electronic tablet and digital measurement-feedback system. We used strategies that promoted visibility of screening progress and sharing of data with hospital administration. Descriptive statistics were used to assess prevalence of clinically significant symptoms of anxiety and depression and symptom severity within our sample. RESULTS: Over the first 2 years of the project, we exceeded our goal of screening 80% of eligible patients per year (80%-95% screened) and are on a similar trajectory within the first 7 months of year 3. We identified high prevalence of clinically significant symptoms of depression (16%) and anxiety (14%) similar to those found in other chronic illness populations. These data helped us advocate hospital leadership to support the development of new mental health services to address identified needs at our center. CONCLUSION: Leveraging coproduction to address stakeholder needs led to successful implementation of a sustainable MHS process.

Total Synthesis of the Highly N-Methylated Acetylene-Containing Anticancer Peptide Jahanyne.

The first total synthesis of the highly N-methylated acetylene-containing lipopeptide jahanyne, an apoptosis-inducing natural product from marine cyanobacteria, is reported. A late-stage solution-phase coupling enabled introduction of the C-terminal ketone pyrrolidine moiety. A modified Fmoc solid-phase synthesis strategy was adopted to effectively couple multiple sterically hindered N-methylated amino acids while suppressing epimerization. The total synthesis has enabled confirmation of the proposed absolute configuration of natural jahanyne.

[Sentinel node in the surgical treatment of the breast cancer. Technique and clinical experience]. / Il linfonodo sentinella nel trattamento chururgico del carcinoma del mammella. Principi di tecnica ed esperienza clinica.

AIM: It is very important to confirm the reliability of the sentinel node (SN) technique in breast cancer surgery, since it can avoid useless traumas, wide mutilations, prolongation of the operation. The aim of the study is to give a contribution to evaluate the real value of SN as regards axillary lymph nodes, in breast cancer, in order to limit axillary lymphadenectomy (AL). METHODS: The search of LS was made in 42 patients (using Patent Blue alone in 5 cases, with radioisotope in 25 cases and with both techniques in 12 cases); their mean age was 62 years and they were suffering from not multicentric infiltrating carcinoma of the breast, with a diameter less than the 2.5 cm and no evidence of axillary gland at clinical examination. All the patients underwent histologic examination of SN and AL was carried out, whatever was the histologic result of SN. RESULTS: Lymphoscintigraphy identified the SN in 96% of the cases (1 case with no identification in a patient with a previous excisional biopsy), with the Patent Blue in 80% of the cases and with the combined technique in 100% of the cases. The average number of SN obtained was 3 and the number of removed lymph nodes in AL was 25. The metastasization of SN was verified in 10 cases, in 3 of them the SN turned out to be the only one interested by metastasis. In 1 case the intraoperative examination was negative and the postoperative one was positive. The percentage of false-negative was 5% (1 case with lymphoscintigraphy and 1 case with Patent Blue). These findings show that in about 70% of the patients AL could be avoided since axillary lymph nodes were without metastases. The predictive role of SN, particularly with lymphoscintigraphy, proved to be reliable with a very reduced number of false-negative. CONCLUSIONS: In our opinion, the SN technique can be considered reliable but it could be used in routine practice when all false-positive can be avoided, since even if not very numerous they represent the principal obstacle to its application.

[Breast-conserving surgery in breast cancer]. / La chirurgia conservativa nel cancro della mammella.

Breast-conserving surgery is the treatment of choice for the breast cancer T < 3 cm. The local recurrence is a problem of diagnosis and consequent treatment. We enrolled, from 1987 to 2004, 1504 breast cancer. In 803 (53.4%) tumor with T < 3 cm we performed conserving surgery. The sentinel lymph node (SN) technique induce to limit the axillary dissection in patients T1a-b to the SN only if non metastatic and located to the first level, the dissection of the 1st level of the axilla in patients T1c-T2 < 3 cm and SN negative, complete axillary dissection in patients with metastatic SN or located to the 2nd level. Our percentage of local recurrence in the follow-up was 3.5% at 5 years and 6% at 10 years.

Prostaglandin E1 versus lumbar sympathectomy in the treatment of peripheral arterial occlusive disease: randomised study of 86 patients.

BACKGROUND AND AIM: The aim of this study was to compare the effects of a pharmacological and a surgical vasodilatatory therapy in the treatment of chronic arterial diseases of the lower limbs. METHODS AND RESULTS: After giving their informed consent, 40 patients were randomised to receive a slow (approximately 2-hour) infusion of 40 microg of prostaglandin E1 twice daily for 28 days (group A), and 46 were randomised to undergo lumbar sympathectomy, including the second and third ganglion. Twenty-four (60%) of the patients in group A experienced complete remission, seven (17.5%) were partial responders, and nine (22.5%) failed to respond. Of the 46 patients in group B, 29 (63%) experienced complete remission, seven (15.2%) were partial responders, and 10 (21.7%) failed to respond. CONCLUSIONS: Broadly similar results were obtained with the two types of treatment, both of which are indicated mainly in Fontaine stages IIB and III (non-advanced), particularly when revascularising therapy is impossible or excessively risky. The two strategies can be advantageously combined with direct revascularisation surgery and may therefore constitute a first-line approach favouring subsequent therapy.

[Preoperative radiotherapy in locally advanced rectal cancer: risks and complications?]. / La radioterapia preoperatoria nel cancro rettale localmente avanzato: rischi e complicanze?

Adjuvant radiotherapy in advanced rectal cancer is currently considered of interest: preoperative radiotherapy in particular seems to provide better results. However, doubts in its use arise from fear of technical difficulties at surgery and increase of complications. In Authors' opinion, though, preoperative radiotherapy associated with perineal omentoplasty represents a real progress in the management of rectal cancer. Preliminary experience supports this feeling.

[Thymopentin and immune response in patients with cancer]. / Timopentina e risposta immunitaria nel paziente neoplastico.

The results of an experimental study using thymopentin (Timunox) on cancer patients are reported. The drug was administered to 25 patients with cancers of the digestive tract in the form of subcutaneous injections of a vial of the product on alternate days for 36 days. All patients treated revealed a good immune response as indicated by assays of total lymphocytes, T4 lymphocytes the T4/T8 ratio and skin tests, apart from their excellent postoperative recovery. Timunox is therefore considered effective in improving the immune competence of cancer patients.