Melatonin as a radioprotective agent: a review

Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, is well known for its functional versatility. In hundreds of investigations, melatonin has been documented as a direct free radical scavenger and an indirect antioxidant, as well as an important immunomodulatory agent. The radical scavenging ability of melatonin is believed to work via electron donation to detoxify a variety of reactive oxygen and nitrogen species, including the highly toxic hydroxyl radical. It has long been recognized that the damaging effects of ionizing radiation are brought about by both direct and indirect mechanisms. The direct action produces disruption of sensitive molecules in the cells, whereas the indirect effects ( approximately 70%) result from its interaction with water molecules, which results in the production of highly reactive free radicals such as *OH, *H, and e(aq)- and their subsequent action on subcellular structures. The hydroxyl radical scavenging ability of melatonin was used as a rationale to determine its radioprotective efficiency. Indeed, the results from many in vitro and in vivo investigations have confirmed that melatonin protects mammalian cells from the toxic effects of ionizing radiation. Furthermore, several clinical reports indicate that melatonin administration, either alone or in combination with traditional radiotherapy, results in a favorable efficacy:toxicity ratio during the treatment of human cancers. This article reviews the literature from laboratory investigations that document the ability of melatonin to scavenge a variety of free radicals (including the hydroxyl radical induced by ionizing radiation) and summarizes the evidence that should be used to design larger translational research-based clinical trials using melatonin as a radioprotector and also in cancer radiotherapy. The potential use of melatonin for protecting individuals from radiation terrorism is also considered.     

Leptospirosis: a report on a series of five autochthonous cases in a Greek region

Leptospirosis is a worldwide zoonotic disease difficult to diagnose both to the clinic and the laboratory. Many risk factors have been involved, such as planting, hunting, harvesting and butchering or sports, such as rafting. We reported our experience through a period of 20 months and we tried to investigate prognostic factors predicting clinical outcomes. Five male patients were admitted to our Department with a median age of 40 years. Overall, three out of five patients presented to other hospital and were transferred to ours with a wrong or delayed diagnosis. In terms of clinical signs and symptoms, all presented with fever, myalgia, headache and jaundice, whereas conjunctival suffusion was present in 80% of them. Acute renal injury and liver deficiency were diagnosed in all subjects. Acute renal failure management required dialysis in 3/5 patients, whereas renal recovery was achieved soon after clinical improvement. However, clinical awareness and serology are the most important tools for accurate and quick diagnosis in order to administer the appropriate therapy.     

Lung cancer as a cardiotoxic state: a review

As the overall survival of patients with lung cancer continues to increase, more cancer survivors are faced with the risk of developing treatment-related cardiovascular toxicities. The increased knowledge of the molecular biology of non-small cell lung cancer has led to new and more personalized treatments. Nevertheless, the usual chemotherapy schemes and radiation therapy induce cardiac toxicities that are frequently underappreciated or go unnoticed. Up to date, the majority of cardiotoxicity studies have been focused in breast cancer, but new treatments in lung cancer patients, such as immune checkpoint-blocking antibodies or tyrosine kinase inhibitors, may also exert these cardiac toxic effects and therefore demand of the close collaboration of oncologists and cardiologists, in order to be addressed. The aim of this review is to provide more detailed information in regard to drug-induced cardiac toxicity focused in non-small cell lung cancer patients.     

ALKoma: a cancer subtype with a shared target

Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that is currently the focus of much attention in oncology. ALK is rendered oncogenic as a result of its fusion to NPM1 in anaplastic large cell lymphoma, to TPM3 or TPM4 in inflammatory myofibroblastic tumor, to EML4 in non-small cell lung carcinoma, and to VCL in renal medullary carcinoma. It is also activated as a result of missense mutations in neuroblastoma and anaplastic thyroid cancer. Whereas these various tumors arise in different organs, they share activated ALK, and a marked clinical efficacy with ALK inhibitors has already been shown for some of the tumors with ALK fusions. One of such compound, crizotinib, is now approved in the United States for the treatment of lung cancer positive for ALK rearrangement. I propose that tumors carrying abnormal ALK as an essential growth driver be collectively termed "ALKoma."     

Using a Culture Committee to Improve and Maintain a Positive Workplace Environment During a Pandemic

Workplace culture is often overlooked in interventions to improve the delivery of health care efficiency. Burnout and employee morale have been longstanding issues in health care and can negatively affect both provider and patient health. To address employee wellness and promote department unity, a culture committee was established within a radiation oncology department. After the emergence of the COVID-19 pandemic, burnout and social isolation among health care workers have increased substantially, affecting job performance and stress levels. This report revisits the efficacy of a workplace culture committee 5 years after its establishment, while also outlining its role during the pandemic and in the transition to a peripandemic workplace. The initiation of a culture committee has been pivotal to identifying and improving workplace stressors that may enable burnout. We suggest health care environments implement initiatives that encompass tangible and actionable solutions to feedback provided by employees.     

Acute appendicitis as a sign of a colorectal carcinoma

The relationship of acute appendicitis occurring previous to cancer in colon and rectum was studied in the consecutive records of 561 patients, of 40 years of age and older, operated upon with an appendectomy because of acute appendicitis. Sixteen (2.9%) of these patients were readmitted within three years because of a carcinoma in colon or rectum. The incidence of carcinoma in the colon and rectum in the population, of the same age, is only 0.1%, according to the Swedish Cancer Registry (1). This difference is statistically significant. Where acute appendicitis and colon carcinoma co-exist, the danger is that the carcinoma may be missed. Therfore, any patient over the age of 40 presenting with acute appendicitis should be carefully checked for carcinoma in the colon.     

Osteopontin: a new role for a familiar actor

Our understanding of the events that occur in cancer progression has been enhanced by the use of cell lines in vitro. Changes in gene expression, induction of signalling, and cell motility can all be investigated in this setting. However, other aspects of progression can be revealed only in vivo, especially the interactions of tumour cells with host cells and organ systems. In one such in vivo model, described by McAllister and colleagues, it proved possible to establish a novel function of an already well-characterised protein, osteopontin, adding to its attractiveness as a target in cancer therapy.     

Adenovirus E1a as a tumor-suppressor gene.

The E1a gene of group C adenoviruses is one of the most studied transforming genes of DNA tumor viruses. These transforming genes have been conventionally considered as dominant oncogenes since they transform cells in vitro and many of the resulting transformed cell lines induce tumors in experimental animals. It now appears that, in addition to its well-known transforming activities, E1a possesses activities which suppress transformation, tumorigenesis and malignant progression (metastasis) of tumor cells. Thus, E1a appears to meet the definition of both a dominant oncogene and a tumor-suppressor gene.     

fosB is a transforming gene encoding a transcriptional activator

The fosB gene encodes a nuclear protein that shows a high degree of homology with c-Fos in several of the known functionally crucial domains, e.g., the leucine zipper and the DNA-binding site, but shows considerable divergence in other regions. Here, we report that FosB, when placed under the control of a constitutive promoter, exhibits clear transforming properties in focus assays using mouse NIH3T3 or rat 208F fibroblasts. The transforming potential of FosB is considerably stronger than that of a corresponding c-fos construct and resembles that of viral fos genes. Using chimeric fos/fosB constructs we show that the C-terminal half of FosB is responsible for these stronger transforming properties, apparently by giving rise to significantly higher levels of protein as compared with the corresponding c-fos sequence. Surprisingly, substitution of the N-terminus of Fos with that of FosB decreases its transforming potential. These differences in the transforming potential are not related to DNA or protein expression, but rather seem to reflect differences in the molecular function(s) encoded in the N-terminal halves of Fos and FosB protein. Both, fosB- and v-fos transformed cells show increased expression of a number of endogenous genes, including c-jun, transin, alpha 1(III) collagen and tissue plasminogen activator. Transactivation by FosB and v-fos of the c-jun and alpha 1(III) collagen gene promoters and of a 3 x TRE-tk chimeric promoter could be shown in transient CAT assays. v-Fos, but not FosB-transformed cells, also show elevated levels of urokinase and plasminogen activator inhibitor mRNAs, pointing to potential differences in the gene regulatory properties of the two Fos family members.     

DBT as a Screening Tool and a Diagnostic Tool

Purpose of Review

The purpose of this study is to review recent and classic references on digital breast tomosynthesis to evaluate the clinical utility of the technology in both the screening and diagnostic evaluation of women.

Recent Findings

Multiple large-scale studies have demonstrated reduction in recall rate and increase in cancer detection. Digital breast tomosynthesis (DBT) has been shown to be especially valuable for specific patient populations, including those under age 50, and those with dense breast tissue. Additionally, DBT can be of great benefit with the evaluation of specific lesion types, including spiculated masses and asymmetries. DBT has also shown value in the diagnostic evaluation of patients.

Summary

DBT has proven benefits for use in breast imaging. This article will discuss the utilization of DBT as a tool in the evaluation of patients in both the screening and diagnostic setting.

     

Clinical Research of a Modified Midfacial Degloving in a Maxillectomy （with a Report of a Typical Case）

OBJECTIVE To investigate the feasibility of employing a modified midfacial degloving in maxillectomy. METHODS Eight patients with carcinoma of the maxillary sinus underwent a modified midfacial degloving operation.The tumors were classified according to the 2002 AJCC system.The TNM staging of the cases was as follows:1 T4aN0M0,2 T3N0M0 and 5 T2N0M0.Of the 8 cases,1 patient underwent extended maxillectomy;exenteration of the orbit;tumorectomy of the sphenomaxillary and infratemporal fossae.Two patients received a total maxillectomy,and 5 a partial resection of the maxilla. Postoperative pathological report:4 well-di?erentiated squamous carcinoma,2 moderately-differentiated squamous carcinoma,1 mucoepidermoid carcinoma and 1 adenoid cystic carcinoma. RESULTS A modified midfacial degloving operation can sufficiently expose a field of operation,resect the tumor within a safe margin,and leave no facial cicatricles.One patient died of intracranial metastasis 8 months a er operation.We observed no recurrences or metastasis in other patients during the period of follow-up. CONCLUSION The major advantages of employing the modified midfacial degloving in maxillectomy is that a facial incision can be avoided.It has an advantage of minimal invasive surgery.     

Pleurodesis in recurrent pleural effusions: a randomized comparison of a classical and a currently popular drug

STUDY OBJECTIVES: Pleurodesis is generally regarded to give the best palliation in recurrent pleural effusion. Talc is now increasingly recommended but in our department quinacrine has been used successfully for many decades with good results and only minor side effects. It was therefore decided to make a prospective randomized clinical study comparing quinacrine (500 mg) with talc (5 g) with regard to efficacy and safety. METHODS: One hundred and ten eligible consecutive patients with recurrent and or malignant effusions, from 1 March 1996 till 31 March 1999 were randomized to chemical pleurodesis with either talc or quinacrine through a chest drainage tube after medical thoracoscopy. Patients were evaluated with chest radiographs at 2 weeks and 2, 4, and 6 months after pleurodesis. RESULTS: Chi-square test showed 84% power to distinguish between the groups and 10% to determine the primary endpoint. Primary success (fluid production < 50ml/24h within the first 6 days) was 96% of 56 patients with talc and 91% of 54 patients with quinacrine, a non-significant difference (P = 0.46). Quinacrine patients needed a repeated treatment in 31% (17 patients) and talc patients in 7% (4 patients) (P < 0.05). Side effects were minor with no significant difference between the substances. CONCLUSIONS: Both substances are effective. Talc treatment had less often to be repeated. This indicates that the recommendation of talc for pleurodesis is well founded. However, quinacrine is a good alternative.     

Outpatient parathyroidectomy: a new paradigm from a nursing perspective

PURPOSE OF REVIEW: Nursing assessment and management regarding the care of patients with primary hyperparathyroidism (1 degrees HPTH) has evolved in parallel with the marked changes in diagnosis and surgical approach to the disease. Earlier diagnosis and vast advancements in surgical approach has shifted the paradigm of nursing intervention into the outpatient setting. RECENT FINDINGS: The early detection of 1 degrees HPTH has become more prevalent in the preceding three decades. The clinical profile has shifted to minimally symptomatic or asymptomatic patients who have excess serum PTH levels, along with hypercalcemia. A recent consensus conference proposed diagnostic guidelines relevant to the decision making process regarding the advisability of surgical intervention vs. medical management. With surgical intervention as the only definitive treatment for 1 degrees HPTH, the successful outcomes associated with outpatient minimally invasive parathyroidectomy have shifted the patterns of recommendation for surgery, even within the group of asymptomatic patients. SUMMARY: The endocrine nurse is integral in the successful team management of patients diagnosed with 1 degrees HPTH. From a nursing perspective, the paradigm has shifted from an inpatient focus centered around the progressive clinical signs and symptoms of the disease, to a comprehensive patient care model of assessment, education, and pre, peri and postoperative monitoring of patients who benefit from the demonstrated positive outcomes associated with parathyroid surgery in the outpatient setting.     

Cantuzumab mertansine in a three-times a week schedule: a phase I and pharmacokinetic study

PURPOSE: Cantuzumab mertansine (SB-408075; huC242-DM1) is a conjugate of the maytansinoid drug DM1 to the antibody huC242, which targets CanAg antigen. In previous studies, cantuzumab mertansine was considered safe and tolerable, but transaminitis precluded tolerance of higher doses. Based on those studies, it was suggested that treatment at intervals of the half-life of the intact immunoconjugate may allow a higher dose density. This provided the rationale for the three-times weekly treatment explored in this protocol. METHODS: Patients with advanced solid tumors and documented CanAg expression were treated with escalating doses of cantuzumab mertansine IV administered three-times a week in a 3 out of 4 weeks schedule. Plasma samples were assayed to determine pharmacokinetic parameters. RESULTS: Twenty patients (pts) with colon (11/20), rectal carcinomas (2/20), or other malignancies (7/20) were treated with doses ranging from 30 to 60 mg/m(2) per day of cantuzumab mertansine IV three-times a week. The maximum tolerated dose (MTD) was 45 mg/m(2), and the dose-limiting toxicity was grade 3 transaminitis. Hepatic, hematologic, and neurosensory effects occurred, but were rarely severe with repetitive treatment at doses of 45 mg/m(2). CONCLUSIONS: Treatment with cantuzumab mertansine at 45 mg/m(2) per day three-times weekly x 3-every-4-week schedule proved that a dose-intense treatment with an immunoconjugate can be safely administered. The pharmacokinetic profile of the intact immunoconjugate indicates that the linker is cleaved with a half-life of about 2 days, resulting in faster clearance of the maytansinoid relative to the antibody. Therefore, with the development of second-generation immunoconjugates, there is a need for improvement of the immunoconjugate linker to take full advantage of the slow clearance of full-length antibody molecules.     

Immunotherapy as a Potential Treatment for Chordoma: a Review

Chordoma is a locally aggressive primary malignancy of the axial skeleton. The gold standard for treatment is en bloc resection, with some centers now advocating for the use of radiation to help mitigate the risk of recurrence. Local recurrence is common, and salvaging local failures is quite difficult. Chemotherapy has been ineffective and small molecule targeted therapy has had only marginal benefits in small subsets of patients with rare tumor phenotypes or refractory disease. Recent successes utilizing immunotherapy in a variety of cancers has led to a resurgence of interest in modifying the host immune system to develop new ways to treat tumors. This review will discuss these studies and will highlight the early studies employing immune strategies for the treatment of chordoma.     

Radiotherapy for a Phalanx Bone Metastasis of a Lung Adenocarcinoma

Phalanx bone metastasis as the initial presenting sign of lung cancer is a rare presentation. Lung cancer is known to metastasize to the bone, but rarely to the fingers. A 61-year-old male smoker presented with pain in the left ring finger. Severe pain discouraged the patient from using his left hand. An X-ray of the left hand showed a lytic bone lesion. The patient was treated with finger radiotherapy. Analgesics were no longer needed and the patient was able to reuse his left hand in his everyday life. Palliative radiotherapy relieved our patient and improved his quality of life.Key words: Acrometastasis, Phalanx, Lung adenocarcinoma, Radiotherapy, Pain relief     

Dermatofibrosarcoma protuberans: a surgical disease with a molecular savior

PURPOSE OF REVIEW: Dermatofibrosarcoma protuberans is a low-grade malignancy of the skin and subcutaneous tissues with low potential for the development of distant metastases. This tumor is characterized by infiltrative growth, and a chromosomal translocation involving the COL1A1 gene on chromosome 17 and the gene platelet-derived growth factor B gene on chromosome 22. This review will examine recent data confirming the central role of surgery in managing this disease and new findings for the application of molecularly targeted therapy in patients with unresectable disease. RECENT FINDINGS: The largest published series of dermatofibrosarcoma protuberans cases has reported that surgery can lead to excellent local control in dermatofibrosarcoma protuberans in over 95% of cases. In patients with metastatic disease, or with locally advanced disease not suitable for surgical excision, inhibition of platelet-derived growth factor receptors with imatinib (Gleevec) can lead to striking clinical results, including complete responses in some patients. SUMMARY: The identification of platelet-derived growth factor B as a near universal translocation partner in chromosomal rearrangements in dermatofibrosarcoma protuberans has led to the successful application of therapy targeted at platelet-derived growth factor receptors. Although wide surgical excision remains the standard of care, patients with locally advanced disease not suitable for wide surgical excision or with metastatic disease can be managed with the platelet-derived growth factor receptors inhibitor imatinib with high probability of response.