Anti-PEc: Development of a novel monoclonal antibody against prostate cancer.

BACKGROUND: The Ec peptide (PEc) that defines the IGF-1Ec isoform, is associated with prostate cancer progression by inducing proliferation, metastases, and tumour repair. On these grounds, an anti-PEc monoclonal antibody (MAb) was developed. Our objective is to examine the effects of this antibody on prostate cancer and its possible side effects. METHODS: The effects of the obtained MAb were examined in cancer and non-cancerous cell lines (unmodified and modified either to overexpress or silence PEc) and in tumours in SCID mice injected with unmodified prostate cancer cells. The investigation was obtained with respect to cellular proliferation, migration, invasion, toxicity to tumours, effects on the cell cycle, immune response activation, effects on mesenchymal stem cell mobilisation leading to tumour repair, tissue distribution, and toxicity to mice. RESULTS: Anti-PEc MAb treatment led to a significant decrease in cellular proliferation, migration, and invasion compared to the untreated cell lines (p < 0.0005 in every case). Mechanistically, these effects were associated with the downregulation of pERK1/2 and vimentin and the upregulation of E-Cadherin. In vivo, anti-PEc MAb treatment was associated with a significant decrease in tumour size and metastases rate (p < 0.0005 in every case) by reversing the tumours mesenchymal phenotype. It also inhibited host stem cell mobilisation towards the tumour, leading to apoptosis. Anti-PEc MAb assessment in respect to distribution and toxicity, indicated its tumour specificity and lack of toxicity. CONCLUSIONS: These data indicate that the therapeutic targeting of PEc with the anti-PEc MAb may have considerable clinical benefit for prostate cancer patients.

Case report of crusted scabies, brief review of its pathophysiology and latest data.

Background: Crusted scabies is a rare form of parasitic infection provoked by a massive infestation of the ectoparasite Sarcoptes scabiei varietas hominis on human skin. It is an extremely contagious type of disease and can even lead to a social stigma. In European countries like Greece, many cases remain undiagnosed for long periods, causing extreme distress in the patient's everyday life and social environment. Case Description: Herein, we present a case of an 86-year-old woman with crusted scabies in Greece, who remained undiagnosed for 5 months. Massive hyperkeratotic plaques on the extremities, and face, palmoplantar keratoderma, and numerous small erythematous papules on the torso with extreme itch were the main clinical manifestations of the patient. Dermoscopy revealed the parasite. All necessary decontamination measures were taken by personnel. Treatment was administered and a complete cure of the disease was observed. Conclusions: In this case, the use of dermoscopy has attributed to precise crusted scabies diagnosis and acute pharmacological management of the patient. Early diagnosis of such diseases not only saves patients from lethal secondary infections, but also reduces the risk of a massive scabies outbreak. We also conducted a mini-review, analyzing all recent data concerning crusted scabies macroscopic, dermatoscopic, and histological images. All new information concerning the pathophysiological mechanism of crusted scabies manifestation, updated treatment options, and potential resistance to widely-used treatments are provided.

Unveiling the Immune Microenvironment's Role in Breast Cancer: A Glimpse into Promising Frontiers.

Breast cancer (BC), one of the most widespread and devastating diseases affecting women worldwide, presents a significant public health challenge. This review explores the emerging frontiers of research focused on deciphering the intricate interplay between BC cells and the immune microenvironment. Understanding the role of the immune system in BC is critical as it holds promise for novel therapeutic approaches and precision medicine strategies. This review delves into the current literature regarding the immune microenvironment's contribution to BC initiation, progression, and metastasis. It examines the complex mechanisms by which BC cells interact with various immune cell populations, including tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Furthermore, this review highlights the impact of immune-related factors, such as cytokines and immune checkpoint molecules. Additionally, this comprehensive analysis sheds light on the potential biomarkers associated with the immune response in BC, enabling early diagnosis and prognostic assessment. The therapeutic implications of targeting the immune microenvironment are also explored, encompassing immunotherapeutic strategies and combination therapies to enhance treatment efficacy. The significance of this review lies in its potential to pave the way for novel therapeutic interventions, providing clinicians and researchers with essential knowledge to design targeted and personalized treatment regimens for BC patients.

Pinnae and facial hypertrichosis induced by cetuximab.

INTRODUCTION: Anti-EGFR targeted anti-cancer treatment is associated with various skin adverse events. Cetuximab is often associated with acneiform papules and skin disorders. Hypertrichosis cited in face pinnae and eyelash trichomegaly are seldom described. CASE REPORT: A 72-year-old female cancer patient presented deteriorating facial-pinnae hypertrichosis and eyelash prolongation post cetuximab infusion. MANAGEMENT AND OUTCOME: Consecutive cetuximab administration led to exaggerating hairy skin side effects, fully alleviated when the drug was discontinued. DISCUSSION: To the best of our knowledge, this is the first reported case of an anti-EGFR-associated diffuse pinnae hypertrichosis presentation in a female patient in literature. This distinct entity can be easily diagnosed and manipulated with early drug withdrawal. An extensive review of relevant basic molecular research is provided to increase physicians' awareness.

Lichenoid drug eruption associated with imatinib mesylate therapy.

INTRODUCTION: Imatinib Mesylate (IM), a tyrosine kinase inhibitor, has been reported to cause several adverse reactions, most of them with cutaneous involvement. Non- Lichenoid IM associated skin reactions have been sufficiently- recorded. To our knowledge, Lichenoid Drug Eruption (LDE) is recorded in a minority of registries. CASE REPORT: To describe an LDE induced case by IM treatment. TREATMENT AND OUTCOME: Histological Confirmation and promptly dermatological consultation relieved successfully the cutaneous adverse event. DISCUSSION: Ongoing expansion of IM usage in a wide spectrum of new indications is more likely to make physicians experience such LDE cutaneous side effects more often. Hence, they should be highly suspicious to early detect these distinct histologic entities, handle these undesired complications and guarantee satisfactory immediate outcomes, avoiding frivolous IM dosage modifications.

Immune Checkpoint Inhibitors' Associated Renal Toxicity: A Series of 12 Cases.

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary "lupus-like" membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with "lupus-like" nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.

Health-Related Quality of Life and Social Support of Elderly Lung and Gastrointestinal Cancer Patients Undergoing Chemotherapy.

Introduction: Increasing life expectancy has led to a higher incidence of cancer in the elderly, thus making them vulnerable and worsening their health-related quality of life (HRQoL) and their need for support. Objective: The aim of this study was to examine the HRQoL and social support in elderly Greek lung and gastrointestinal cancer patients undergoing chemotherapy. Methods: This was a descriptive, cross-sectional study of 104 elderly cancer patients, who were receiving chemotherapy in the outpatient department and inpatient ward of a General Hospital in Athens. The data were collected using purposive sampling between December 2019 and May 2020, and included demographic and clinical characteristics, the HRQoL questionnaire, Short Form 36 (SF36), and the Personal Resource Questionnaire (PRQ-2000). Results: The participants' median age was 72 years; the majority were male (62.5%) and had lung cancer (57.7%). The SF36 data revealed a relatively moderate (42.7-62.61) HRQoL in most subscales. The "Pain" subscale recorded the highest score (75.0), and the "social function" subscale the lowest (42.79). The PQR-2000 indicated a satisfactory level of social support (81.65), with values ranging between 48 and 105; married patients with higher education scored more highly (p < .05). Patients aged 65-75 years reported better HRQoL and greater social support than older patients. In addition, patients with their own family and a relatively high income reported better HRQoL and social support compared to single individuals, with low income, who were cared for by their children. Positive and statistically significant (p < .05) correlations were found between the SF36 subscales of role functioning/physical, vitality, general health, emotional well-being and the PRQ-2000. Conclusion: The HRQoL and social support of elderly cancer patients positively affect the course of their health. Healthcare systems and social services should address the multiplying needs of these patients with targeted interventions to support their well-being.

Cutaneous Stevens Johnson - Toxic Epidermal Necrolysis Immunotherapy related Toxicities in Lung Cancer Patients.

INTRODUCTION: New Immuno- Checkpoint inhibitors (ICIs) functioning as PD-1- PDL-1 blockers are nowadays used in a majority of anticancer treatments. Many immune- related Adverse Events (irAEs) are published daily; severe skin toxicities, Stevens Johnson/ Toxic Epidermal Necrolysis (SJS/TEN) are seldom reported. CASE REPORT: Herein, we present two interesting skin sever toxicity cases of lung cancer patients, undergoing PD-1- PDL-1 Immunotherapy. In both cases, a morbilliform rash with documented histological Toxic Epidermal Necrolysis Pattern /Stevens Johnson findings, was thoroughly studied. MANAGEMENT & OUTCOME: Both cases were therapeutically managed according to guidelines with different outcome. DISCUSSION: Two focused cases of irAEs, is the rationale, to briefly review mechanisms of major toxicities caused by PD-1/PD-L1 blockade, and present all new data in their precise management. ICIs' association with SJS/ TEN still remains unclear; underlying urgent need for further studies. It is important to alert physicians to promptly identify life threatening irAEs. Being familiar, provides management efficacy, safe resolve and encourage beneficial balanced cost effective treatments.

Replication Protein A (RPA1, RPA2 and RPA3) expression in gastric cancer: correlation with clinicopathologic parameters and patients' survival.

PURPOSE: Replication Protein A (RPA) consists of three subunits (RPA1, RPA2 and RPA3) essential for all major DNA metabolic pathways. Although RPA seems to be a promising therapeutic target, its role in human cancers has not been fully elucidated. This is the first study investigating the expression of all the three RPA subunits in a series of 74 resected gastric carcinomas and analyzing the possible correlations with clinicopathologic parameters (histological type, grade, lymphovascular invasion, lymph node status and disease stage), Ki-67 proliferative index, Topoisomerase IIa expression and patients' survival. METHODS: Immunohistochemistry using monoclonal antibodies. Univariate and multivariate statistical analysis. RESULTS: All the three subunits showed widespread nuclear expressions in gastric carcinomas with significant associations among their expressions. RPA2 demonstrated higher expression levels in low grade carcinomas and a gradual significant decrease from N0 to N3 and from stage I to stage IV carcinomas. All the three subunits were statistical significantly more abundant in lymph node negative and earlier stage (stage I & II) gastric carcinomas. No associations were established among RPAs and the proliferative marker Ki-67. In patients with positive lymph nodes and advanced tumor stage, RPA1 expression seemed to predict a better overall survival implying a probable predictive role. CONCLUSIONS: The widespread expression of RPA(1-3) suggests one or more roles in gastric cancer. Their presence in earlier stage tumors probably offers an opportunity for early targeted therapy. Their probable predictive value in node positive and advanced stage tumors needs further investigation with respect to specific chemotherapeutic treatments.

Primary squamous cell carcinoma of the pleura treated with nivolumab.

Malignant pleural effusions usually manifest in the course of metastatic cancer disease. Primary pleural tumours are rare with mesothelioma being by far the most common. Primary squamous cell carcinoma of the pleura (PSCCP) is extremely rare. It is usually asymptomatic, until it invades the pleura presenting pain as the first symptom. Our knowledge about its treatment or prognosis is limited due to its rarity. We present the case of a 48-year-old man who presented with persistent right-sided thoracic pain with chest computed tomography (CT) scan demonstrating a right-sided pleural effusion and pleural mass invading the ribs. Ultrasound-guided biopsy revealed a PSCCP. Positron emission tomography staging demonstrated metastatic lung and lymph node involvement precluding surgical therapy. We provide information about treatment, including immunotherapy as well as extended follow-up course. Immunotherapy with nivolumab resulted in prolongation of survival with good quality of life.

Early tumor-cell gene expression changes may predict the response to first-line bortezomib-based therapy in patients with newly diagnosed multiple myeloma.

PURPOSE: Maximizing the response rate to first-line therapy in patients with multiple myeloma (MM) is important because it leads to improved outcome. Gene-expression studies have identified prognostic gene sets in patients receiving bortezomib-based therapy. Comparison of the lists of genes derived from two gene-expression-based models (GEP70, GEP80) showed that they overlap in three genes, namely PSMD4, BIRC5, and KIAA1754. An unanswered question is whether early gene-expression changes can be used as predictors of the response to first-line bortezomib. In this study we aimed to examine the predictive value of gene expression changes for the depth of response after bortezomib-based therapy in newly diagnosed MM. METHODS: We prospectively assessed the relation between early PSMD4, BIRC5, and KIAA1754 gene expression changes (before therapy and one week later) and the response rate after bortezomib-based therapy in 25 patients with newly diagnosed MM. Gene expression was studied by RT-PCR on CD138-selected plasma cells, and changes were recorded as upregulation, downregulation, or unchanged. RESULTS: Whereas baseline prognostic factors including genetic lesions and stage were not predictive of the response rate, we found that early BIRC5 and KIAA1754 gene-expression changes were significantly associated with the depth of response to bortezomib (p=0.001 and p<0.001, respectively). PSMD4 was not predictive of the depth of response. KIAA1754 upregulation was linked to complete remission (CR) or very good partial remission (VGPR). BIRC5 upregulation was linked to stable disease (SD) or progressive disease (PD). We also observed that BIRC5 upregulation was associated with worse progression-free survival (PFS). CONCLUSIONS: Our results suggest that BIRC5 and KIAA1754 gene-expression changes may predict the response to bortezomib-based therapy. These data may have relevance for the stratification and early adaptation of first-line treatment in patients with newly diagnosed MM.

Adrenocortical oncocytic carcinoma with recurrent metastases: a case report and review of the literature.

BACKGROUND: Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional pathological entity, since only 22 cases have been documented in the literature so far. CASE PRESENTATION: Our case concerns a 54-year-old man with past medical history of right adrenal excision with partial hepatectomy, due to an adrenocortical carcinoma. The patient was admitted in our hospital to undergo surgical resection of a left lung mass newly detected on chest Computed Tomography scan. The histological and immunohistochemical study revealed a metastatic AOC. Although the patient was given mitotane orally in adjuvant basis, he experienced relapse with multiple metastases in the thorax twice in the next year and was treated with consecutive resections. Two and a half years later, a right hip joint metastasis was found and concurrent chemoradiation was given. Finally, approximately five years post disease onset, the patient died due to massive metastatic disease. A thorough review of AOC and particularly all diagnostic difficulties are extensively stated. CONCLUSION: Histological classification of adrenocortical oncocytic tumours has been so far a matter of debate. There is no officially established histological scoring system regarding these rare neoplasms and therefore many diagnostic difficulties occur for pathologists.

Correlation of androgen receptor status, neuroendocrine differentiation and angiogenesis with time-to-biochemical failure after radical prostatectomy in clinically localized prostate cancer.

UNLABELLED: The aim of this study was to elucidate the prognostic value of the immunohistochemical detection of the androgen receptor (AR) status, the chromogranin A assessment of neuroendocrine differentiation (NED) and the CD34 assessment of microvessel density (MVD) with time-to-biochemical failure among surgically treated patients with clinically localized prostate cancer. PATIENTS AND METHODS: Surgical specimens from 130 patients with clinically localized prostate cancer, treated with radical prostatectomy, were analyzed by immunohistochemistry on paraffin tissue sections. Full-length follow-up records were available for 94 patients. RESULTS: Biochemical failure was observed in 37% of these patients. A statistically significant inverse relationship was observed between AR status and: (i) seminal vesicle invasion and (ii) surgical margin infiltration. Positive association was also detected between NED and: (i) Gleason's score, (ii) extracapsular extension, (iii) seminal vesicle invasion, (iv) surgical margin infiltration and (v) tumour volume. In addition, MVD was related to: (i) Gleason score, (ii) extracapsular extension, (iii) seminal vesicle invasion, (iv) pelvic lymph node metastasis and (v) tumour volume. Kaplan-Meier survival curves confirmed that Gleason score, extracapsular extension, seminal vesicle invasion, pelvic lymph node metastasis, tumour volume, NED, MVD and coexistence of increased NED and MVD may be potential biochemical failure predictors. However, in the multivariate analysis, MVD was the only independent prognostic factor for biochemical failure. CONCLUSION: A high MVD index can estimate the risk for biochemical failure in clinically localized prostate cancer after radical prostatectomy.

Prostate cancer with small-cell morphology: an immunophenotypic subdivision.

OBJECTIVE: To study the immunophenotypic characteristics and clinical outcome of morphologically undifferentiated prostatic carcinoma with small-cell morphology (U-PC-SCM). MATERIAL AND METHODS: Sixteen patients with U-PC-SCM were enrolled. The streptavidin-biotin complex immunohistochemical method was used on paraffin-embedded tissue sections to test positivity for prostate-specific antigen, prostate-specific acid phosphatase, CD57, androgen receptors, CK8-18, epithelial membrane antigen, carcinoembryonic antigen, CD56, neuron-specific enolase, chromogranin, synaptophysin, serotonin, various hormones, thyroid transcriptional factor-1 and Ki-67/MIB1. RESULTS: Based on immunophenotypic criteria, we identified two groups of patients. The final diagnosis was U-PC (Gleason score 10) in Group 1 (n=9) and pure or mixed neuroendocrine small-cell carcinoma in Group 2 (n=7). Group 1 underwent total androgen blockade (TAB) with no major response and had a median survival of 9 months. In Group 2, three patients underwent TAB, two of whom died of progressive disease. The third patient showed a partial response (PR) for 18 months but eventually relapsed with liver metastatic lesions. He was then treated with cisplatin + etoposide and showed a PR for 3 months and survived for 5 months after the initiation of the second-line chemotherapy (CTH) treatment. The other four patients received six cycles of cisplatin + etoposide. There were two complete responses of >14 and >22 months, respectively and 2 PRs of 11 and 17 months, respectively, the partial responders surviving for 14 and 21 months, respectively. CONCLUSION: U-PC-SCM with a neuroendocrine immunophenotype is a histogenetically distinct entity with different clinical and laboratory manifestations which responds well to a cisplatin + etoposide CTH regimen.