Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?

Prostate cancer (PC) is the most common malignancy and the fifth cause of cancer death in men. The treatment for localized or locally advanced stages offers a high probability of cure. Even though the therapeutic landscape has significantly improved over the last decade, metastatic PC (mPC) still has a poor prognosis mainly due to the development of therapy resistance. In this context, the use of immunotherapy alone or in combination with other drugs has been explored in recent years. However, T-cell directed immune checkpoint inhibitors (ICIs) have shown limited activity with inconclusive results in mPC patients, most likely due to the highly immunosuppressive PC tumor microenvironment (TME). In this scenario, targeting macrophages, a highly abundant immunosuppressive cell type in the TME, could offer a new therapeutic strategy to improve immunotherapy efficacy. In this review, we summarize the growing field of macrophage-directed immunotherapies and discuss how these could be applied in the treatment of mPC, focusing on their combination with ICIs.

Augmented Genetic Risk of Thrombophilia in Pediatric Acute Lymphoblastic Leukemia: Case report and Review of Literature

Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children. Venous thromboembolism (VTE) is relatively common in children with acute ALL that usually appears after the diagnosis or during therapy secondary to many associated risk factors. Here in we report for the first time a child who developed cerebral venous sinus thrombosis (CVST) prior to the diagnosis of ALL.

A web-based survey on factors for unvaccination and adverse reactions of SARS-CoV-2 vaccines in Chinese postoperative patients with breast cancer

Background Vaccination against SARS-COV-2 has been the most important strategy for preventing infection of Coronavirus disease 2019 (COVID-19). Breast cancer is the most common malignancy in women, but there is a lack of research on the pandemics in postoperative patients with breast cancer. Objective To investigate the rate and factors for SARS-CoV-2 vaccination and adverse reactions after vaccination in postoperative patients with breast cancer. Methods A web-based questionnaire survey on SARS-CoV-2 vaccination in postoperative patients with breast cancer among women. Results A total of 947 online questionnaires were collected. Of these, 341 accepted SARS-CoV-2 vaccination, while 606 were not vaccinated. There were significant differences in age, current treatment, the time since surgery, and the symptoms of anxiety and depression between the two groups. We identified current treatment (OR=0.51 for endocrine therapy; 95% CI: 0.29-0.89), the time since surgery (OR=22.49 for 1-2 years; 95% CI: 12.31-41.10; OR=8.49 for 2-5 years ; 95% CI: 4.98-14.46; OR=1.79 for >5 years ; 95% CI: 1.11-2.89), and the symptoms of depression (OR=2.48; 95% CI: 1.19-5.15) as significant factors for unvaccination. The overall incidence of adverse reactions was 43.1%. The most common local and systemic adverse reactions were pain at the injection site (28.4%) and fatigue (8.8%), respectively. Conclusion Postoperative patients with breast cancer have a relatively lower rate of vaccination for SARS-CoV-2 than the general population. Receiving treatment, a shorter time since surgery and symptom of depression were associated with unvaccination. More importantly, a favorable safety profile of the vaccines is indicated.

Combined effect of heat shock protein inhibitor geldanamycin and free radicals on photodynamic therapy of prostate cancer

Prostate cancer is the most common malignancy and the second leading cause of cancer-induced death among men. Recently, photodynamic therapy (PDT) has attracted great attention in prostate cancer treatment because...

Incidental Meckel’s diverticula low grade neuroendocrine tumor coexisting with synchronous sigmoidian and perianal adenocarcinoma

Although rarely, due to the high variability of the possible tissues encountered in it’s wall, the Meckel’s diverticula can represent a site for tumor development in 0,5-3,2% cases. Data in the literature shows that the most common malignancy at this level is represented by neuroendocrine tumors (NET) the observed incidence of neurendocrine tumors and other primary neoplasia, varies between 12-55%. Moreover, the gastro-intestinal tract was the second primary tumor bearer encountered.

Radical or Not-So-Radical Prostatectomy: Do Surgical Margins Matter?

Prostate cancer is the second most common malignancy in men, and prostatectomy is the treatment of choice for most patients with at least low risk of progression. The presence of positive margins in the radical prostatectomy specimen is considered an adverse pathologic feature, and may prompt additional therapeutic intervention in the patients. The absence of a distinct capsule around the prostate and intraoperative manipulations that aim to minimize postoperative adverse effects, complicate its wide removal. Proper handling of the specimen during the gross processing is essential for accurate determination of the status of margins or resection. Positive margins, defined as the presence of neoplastic glands in the highlighted-with-ink margin of resection, range from 6–38%. The surgical technique, surgeon’s expertise and tumor (i.e., grade and stage) and patients’ (i.e., BMI) characteristics affect the rate of margin positivity. Extensive or multifocal and nonanterior/nonapical positive margins are linked with higher recurrence rates, especially in organ-confined disease, underscoring the need for treating these patients more aggressively. In summary, detailed description of the status of the margins should be performed in every pathology report to determine patients’ prognosis and the most appropriate therapeutic plan.

The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

CircSERPINA3 regulates SERPINA3-mediated apoptosis, autophagy and aerobic glycolysis of prostate cancer cells by competitively binding to MiR-653-5p and recruiting BUD13

Background Prostate cancer (PCa) belongs to an epithelial malignancy that occurs in the prostate gland and is the most common malignancy of the male genitourinary system. Referring to related literature, circSERPINA3 has been reported to be up-regulated in PCa. However, its biological function remains unclear. Purpose This study aimed to reveal the specific role and relevant molecular mechanism of circSERPINA3 in PCa. Methods RT-qPCR was used to examine gene expression and functional analyses were conducted to verify the effect of circSERPINA3 on cell apoptosis, autophagy and aerobic glycolysis in PCa cells. Mechanism assays were applied to evaluate the relationship among circSERPINA3/miR-653-5p/SERPINA3/BUD13. Results CircSERPINA3 was verified to be up-regulated in PCa cells and to inhibit cell apoptosis while promoting aerobic glycolysis and autophagy in PCa cells. CircSERPINA3 and SERPINA3 were also testified to bind to miR-653-5p through a line of mechanism experiments. Moreover, it was discovered that circSERPINA3 could stabilize SERPINA3 mRNA via recruiting BUD13. Additionally, SERPINA3 was verified to inhibit cell apoptosis, while promoting aerobic glycolysis and autophagy in PCa cells. Conclusions Our study suggested that circSERPINA3 regulated apoptosis, autophagy and aerobic glycolysis of PCa cells by competitively binding to miR-653-5p and recruiting BUD13. Graphic abstract

Expression of biomarkers vimentin and Metastasis Associated 1(MTA1) protein in different stages of laryngeal cancer and their impacts on survival

Laryngeal cancer is the second most common cancer after the lip and oral cavity cancer ofhead and neck region1. Laryngeal malignancy is the seventh most common malignancy in males in India. Total number of new laryngeal cancer and death from laryngeal cancer have been estimated 12410 and 3760 respectively in 20192. As per last survey available the number of new cases diagnosed and total number of deaths from laryngeal malignancy were 25,460 and 17,560 respectively in 2012 in India3 . The incidence of cancer larynx is 1.26-8.18 per 100,000 populations in different regions of India. Carcinoma larynx constitutes40% of all Head and Neck cancers. Squamous cell carcinoma constitutes 95% of all malignancies of larynx. Glottis being the most common subsite followed by supraglottis and the least common site is the subglottis. There is an increasing incidence rate of this malignancy among middle aged and elderly men and women throughout the world. Expression of Biomarkers at different stages of laryngeal cancers and their impact on survival can play a crucial role in future management of laryngeal malignancies. In spite of having different modalities of treatments like surgery, radiotherapy, chemoradiation, the prognosis of laryngeal malignancies is still poor. The most common adverse factor for laryngeal cancer has been found lymph node metastasis. The process of progression of LSCC is complex and difficult to know it completely. Despite multi-modality therapeutic advances in recent decades, improvements in overall survival and disease free survival is very less. In this study we emphasized the role of expression of biomarkers vimentin and metastasis associated 1(MTA1) protein in different stages of laryngeal cancer and their impacts on survival.

Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer

Background Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy. Methods Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer. Results Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model. Conclusions We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise. Graphic abstract