Development of a novel bi-specific monoclonal antibody approach for tumour targeting

To overcome the disadvantages of bi-specific antibody methodologies in vivo, a novel antibody approach has been designed to improve tumour targeting and effector to target ratio. The technique involves biotinylated anti-CD3 Fab fragments and streptavidinylated anti-tumour monoclonal antibodies (mAbs) that can spontaneously form cross-links. We describe here a method for the direct cross-linking of sulphydryl-conjugated HMFG1 (anti-MUC1 mucin mAb) to streptavidin by sulphosuccinimidyl-4-(N-maleimidomethyl) cyclohexane- 1-carboxylate. Fab fragments generated by papain digestion of the 1452C11 antibody (anti-CD3 mAb without Fc to avoid peripheral activation of T-cells) were biotinylated with NHS-Iminobiotin. MUC1-transfected BALB/c breast cancer cell lines 413BCR and 425CCR and the parental cell line (410.4) were labelled with streptavidinylated mouse anti-MUC1 mucin mAb. BALB/c effector T-cells were separately labelled with biotinylated anti-CD3 Fab fragments (1452C11) and mixed with tumour cells in different effector to target ratios. Percentage of killing was assessed using the 51Cr cytotoxicity assay. Seventy per cent lysis was measured in the case of 413BCR (high MUC1 mucin expressor) and 40% in the case of 425CCR (low expressor) cell line. No lysis was apparent in the MUC1 negative cell line. These results demonstrate that the novel T-cell redirecting approach we have developed can produce effective immune lysis of target cells in vitro. © 1999 Cancer Research Campaig

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours.

This ENETS guidance paper, developed by a multidisciplinary working group, provides an update on the previous colorectal guidance paper in a different format. Guided by key clinical questions practical advice on the diagnosis and management of neuroendocrine tumours (NET) of the caecum, colon, and rectum is provided. Although covered in one guidance paper colorectal NET comprises a heterogeneous group of neoplasms. The most common rectal NET are often small G1 tumours that can be treated by adequate endoscopic resection techniques. Evidence from prospective clinical trials on the treatment of metastatic colorectal NET is limited and discussion of patients in experienced multidisciplinary tumour boards strongly recommended. Neuroendocrine carcinomas (NEC) and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are discussed in a separate guidance paper

Coexistence of a colon carcinoma with two distinct renal cell carcinomas: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present the case of a patient with two tumors in his left kidney and a synchronous colon cancer. While coexisting tumors have been previously described in the same kidney or the kidney and other organs, or the colon and other organs, to the best of our knowledge no such concurrency of three primary tumors has been reported in the literature to date.</p> <p>Case presentation</p> <p>A 72-year-old man of Greek nationality presenting with pain in the right hypochondrium underwent a series of examinations that revealed gallstones, a tumor in the hepatic flexure of the colon and an additional tumor in the upper pole of the left kidney. He was subjected to a right hemicolectomy, left nephrectomy and cholecystectomy, and his postoperative course was uneventful. Histopathology examinations showed a mucinous colon adenocarcinoma, plus two tumors in the left kidney, a papillary renal cell carcinoma and a chromophobe renal cell carcinoma.</p> <p>Conclusion</p> <p>This case underlines the need to routinely scan patients pre-operatively in order to exclude coexisting tumors, especially asymptomatic renal tumors in patients with colorectal cancer, and additionally to screen concurrent tumors genetically in order to detect putative common genetic alterations.</p

The role of neoadjuvant chemotherapy in the treatment of advanced ovarian cancer

Primary cytoreductive surgery followed by chemotherapy represents the current standard treatment for patients with advanced ovarian cancer. Neoadjuvant chemotherapy followed by interval debulking surgery has been proposed as an alternative approach for the initial management of bulky ovarian cancer, aiming at the improvement of surgical efficiency and patients’ quality of life. According to the hitherto published studies, consisting mainly of retrospective observations, neoadjuvant chemotherapy followed by interval cytoreduction appears to improve the prognosis and quality of life in selected groups of patients. The survival outcome in these patients is similar to that of the conventional approach, or even better in some of the cases. Moreover, patients undergoing debulking surgery after having received neoadjuvant chemotherapy had a reduced perioperative morbidity compared to patients undergoing primary cytoreduction. Concurrently, neoadjuvant chemotherapy provides preoperative knowledge of tumor chemosensitivity, hence allowing the surgeon to choose appropriately aggressive treatment. However, until the results of prospective randomized trials become available, neoadjuvant chemotherapy followed by interval surgery should be applied only to individual cases and primarily in the context of clinical trials. Copyright (C) 2005 S. Karger AG, Basel

The sarcoma immune landscape: Emerging challenges, prognostic significance and prospective impact for immunotherapy approaches

Despite significant advances in multidisciplinary treatment strategies including surgery, radiotherapy, targeted therapy and chemotherapy there are yet no substantial improvements in the clinical benefit of patients with sarcomas. Current understanding of the underlying cellular and molecular pathways which govern the dynamic interactions between the tumor stroma, tumor cells and immune infiltrates in sarcoma tissues, led to the clinical development of new therapeutic options based on immunotherapies. Moreover, progress of the treatment of sarcomas also depends on the identification of biomarkers with prognostic and predictive values for selecting patients most likely to benefit from these new therapeutic treatments and also serving as potent therapeutic targets. Novel combinations with radiotherapy, chemotherapy, targeted therapy, vaccines, CAR-T cells and treatments targeting other immune components of the tumor microenvironment are underway aiming to bypass known resistance mechanisms. This review focuses on the role of tumor microenvironment in sarcoma, prognosis and response to novel immunotherapies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Progressive muscle relaxation as a supportive intervention for cancer patients undergoing chemotherapy: A systematic review

Background: Many cancer patients use a wide variety of techniques to improve their physical and mental well-being, including relaxation therapy and, specifically, Progressive Muscle Relaxation (PMR). However, there is no strong evidence that supports the efficacy of this technique. Objective: Our aim was to review the evidence regarding the use of PMR as a supportive intervention for cancer patients undergoing chemotherapeutic treatment. Method: Six databases were electronically searched: AMED, the Cochrane Library, MEDLINE, PsychINFO, Scopus, and the Web of Science. After removing duplicates, 700 publications were screened and 57 identified as potentially relevant. The flow of information from record identification to study inclusion was conducted in accordance with the PRISMA statement. Original articles published in peer-reviewed journals that studied the use of PMR as an intervention, were randomized or included a matched control group, and that included patients receiving chemotherapy were included. Studies that combined PMR with other interventions were excluded. The methodological quality of included trials was assessed using the Jadad Scale and the CONSORT guidelines. Results: A total of 5 of the 57 papers fulfilled the preset criteria and were included in our systematic review. Our findings indicate that PMR might improve comfort and reduce the anxiety levels and side effects caused by chemotherapy, with the exception of vomiting. Nonetheless, the quality of all the included studies was extremely low. Significance of results: There is evidence that PMR might have a few benefits for patients undergoing chemotherapy. Still, the small number of studies included and their poor quality limit the significance of our results. Despite the fact that pharmaceutical approaches for controlling side effects might be reaching their full potential and that there might be further usefulness for such integrative treatments as PMR, the need to run more high-quality trials testing the efficacy of this technique is warranted before suggesting its adoption as part of standard cancer care. © 2017 Cambridge University Press

Fertility risk assessment and preservation in male and female prepubertal and adolescent cancer patients

Cancer represents the second cause of death in prepubertal children and adolescents, although it is currently associated with an overall sur-vival rate of 80%-85%. The annual incidence rate is 186.6 per 1 million children and adolescents aged up to 19 years. Both disease and treatment options are associated with life-altering, long-term effects that require monitoring. Infertility is a common issue, and as such, fertility preservation represents an essential part in the management of young patients with cancer who are at risk of premature gonadal failure. This review deals with the up-to-date available data on fertility risk assessment and preservation strategies that should be addressed prior to antineoplastic therapy in this vulnerable subgroup of cancer patients. © the authors, publisher and licensee Libertas Academica Limited