Male Cancer Research Articles

Synthesis and anticancer properties of a hybrid molecule with the testosterone and estradiol head-groups

This is the first report on a unique hybrid molecule made of estradiol and testosterone (TS). This distinctive hybrid molecule (1) was designed to interact with both the estrogen receptor (ER) and the androgen receptor (AR) found in hormone-dependent female and male cancer cells, and was synthesized using ethynylestradiol (17EE) as the estrogenic component and 7α-(4-azido-but-2-enyl)-4-androsten-17β-ol-3-one as the androgenic counterpart in a seven-step reaction with ∼ 26 % overall yield. We reasoned that the dual receptor binding ability could allow 1 to act as an antihormone. This was tested on hormone-dependent and hormone-independent breast cancer (BCa) and prostate cancer (PCa) cells. The antiproliferative activity was also assessed on colon and skin cancer cells. We found that 1 was active against MCF7 (ER + ) BCa cells (IC50 of 4.9 μM), had lower inhibitory potency on LNCaP (AR + ) PCa cells (IC50 > 5 μM) and no effect on PC3 and DU145 (AR-) PCa cells. This suggests that the estrogenic component of 1 can interact with the ER on MCF7 cells more effectively than the androgenic component with the AR on LNCaP PCa cells, possibly due to a suboptimal spacer or linkage site(s). Nonetheless, the hybrid 1 was active against colon (HT-29) and melanoma (M21) cancer cells (IC50 of 3.5 μM and 2.3 μM, respectively), and had low cross-reactivity with the drug- and androgen-metabolizing cytochrome P450 3A4 (CYP3A4, IC50 ≫ 5 µM). These findings demonstrate the anticancer potential of 1 and warrant further explorations on this new type of hybrids.

P-381 Fertility preservation in patients with testicular cancer

Abstract Study question Do the clinical stage and histological characteristics of testicular cancer affect sperm quality? Summary answer Sperm concentration, motility and normal morphology significantly decreased in patients with testicular cancer. However, semen parameters were not significantly associated with tumor histology. What is known already Testicular cancer is rare in most countries, with an incidence ranging from ∼1/100,000 to 10/100,000, and represents about 1% of all cancers in men, but about 60% of all cancers in young males aged between 15 and 35 years. Additionally, the incidence of testicular cancer has doubled in the last 20-40 years. While it is clear that chemotherapy treatment can negatively impact infertility, it is increasingly recognized that male-factor infertility may play a significant role in the overall health status of men, and men with infertility may be at higher risk of developing testicular cancer. Study design, size, duration Retrospective data from 284 males, diagnosed with testicular cancer, undergoing to semen cryopreservation before surgery or chemo- or radiotherapy treatments, from January 2016 to June 2022 at Maternal and Child Department, Gynecology and Obstetrics Unit, Couple Sterility Center at Federico II, University of Naples, were included in the study. Participants/materials, setting, methods All patients signed their informed consent to cryopreservation. In order to have an internal control group coming from the same region, results of semen analysis from male partners of couples with certain female factors (bilateral tubal imperviousness or in case of egg donation) were included in the study. After semen collection and liquefaction, the semen specimens were cryopreserved following manufacturer’s protocol with media conteining TEST-yolk buffer. Main results and the role of chance Overall, taking in to consideration the semen cryopreservation, per WHO 2021 criteria, we observed that the majority of semen parameters of patients with testicular cancer resulted between 5°percentile and 25° percentile. The unique parameter over the 50°percentile was the semen volume. Comparing results from male partners of couples with certain female factors and testicular cancer patients several features were significant different. Especially, semen volume resulted significantly increased in cases respect to the control (p = 0,011). Instead, from microscopic evaluation semen concentration, percentage of total sperm motility and % of spermatozoa with normal morphology appeared significantly decreased in patients with testicular cancer (p = 0,000; p = 0,000; p = 0,002). Based on Histopathological Classification of Testicular Tumors the 59% (168/284) were classified as classic seminoma, 14% (41/284) mixed germ cell tumors including seminomatous and nonseminomatous cell tumors, 13% (38/284) nonseminomatous mixed germ cell tumors, 12% (35/284) nonseminomatous germ cell tumors including 4 cases of teratoma and 30 cases of embryonal carcinoma and 2 cases of cariocarcinoma. However, abnormal semen parameters were not significantly associated with tumor histology. Limitations, reasons for caution No information about semen quality after thawing and ICSI outcome could represent the main limitation for a complete information of the preservation program in these patients. Wider implications of the findings We presented our monocentric experience of oncofertility preservation program with especially attention to testicular cancer patients. Presented data emphasizes the importance of semen monitoring in young men and the fertility preservation in management of the patient. Trial registration number not applicable

P-006 Fertility outcomes in men diagnosed with oncohematological diseases who stored their semen for fertility preservation

Abstract Study question What is the prevalence of conceptions among patients who underwent semen cryopreservation before receiving treatment for oncohematological disease? Summary answer Natural live birth rate after oncohematological treatments is around 38%(95%CI:31-45%), but can rise to 61%(95%CI:54-67%) with the use of frozen semen during ART cycles. What is known already Due to advancements in cancer treatments, there is a growing population of male adult cancer survivors. These individuals are at risk of experiencing treatment-induced infertility, and it is generally advised for them to preserve their semen before starting therapies. However, the details regarding the long-term utilization and effectiveness of frozen sperm samples in this particular population remain unclear. Study design, size, duration The study included males with oncohematological disease who stored semen (1987-2018) at Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico’s Assisted Reproductive Technology Unit in Milan. Data, gathered from records or proactive inquiry, assessed natural and ART conceptions post-treatment. The study also examined semen analysis, parenthood attempts, and the usage rates of stored spermatozoa as primary outcomes. Participants/materials, setting, methods The study is limited to men who meet the following eligibility criteria: i) semen cryopreserved for fertility preservation between 1987 and 2018; ii) diagnosis of oncohematological disease; iii) survival of at least 5 years from cryopreservation. Main results and the role of chance A total of 424 patients who underwent semen cryopreservation for oncohematological diseases were included in the study. The median [IQR] age at the time of sperm banking was 27 [23-33]. The most common indication was lymphoma (86%), and 102 subjects (24%) underwent hematopoietic stem cell transplantation. The median sperm concentration at the time of storage was 54 [20-98] million/ml. Among the participants, 242 (57%) men underwent post-treatment sperm analysis, revealing azoospermia in 87 of them (36%, 95%CI: 30-42%). Of the remaining, only 93 (38%) exhibited normal semen parameters. A total of 188 out of the 424 men included (44%) expressed a desire for childbearing and seventy-one achieved a natural live birth (38%, 95%CI: 31-45%). Eighty-nine individuals used their cryopreserved sperm samples, constituting 21% (95%CI: 17-25%) of the entire cohort. Among these 89 men, 45 experienced at least one live birth (51%, 95%CI: 40-61%). Notably, thirty-three men, despite actively seeking pregnancy, did not utilize their frozen semen. In summary, out of the 188 men interested in fatherhood, a total of 114 achieved a live birth (61%, 95%CI: 54-67%). Limitations, reasons for caution Our study is constrained by the lack of detailed information on the illness status, comorbidities, and specific cancer therapies administered. Furthermore, the data concern a single-center population, potentially limiting the generalizability of the results. Wider implications of the findings Oncohematological disease often require systemic therapies or even hematopoietic stem cell transplantation resulting in a very high percentage of infertile patients These findings support the need to prioritize sperm preservation before therapies in these patients, even in cases who are not candidates for stem cell transplantation in the first instance Trial registration number NA

P-344 Systematic review of the gonadotoxicity and risk of infertility of soft tissue sarcoma chemotherapies in pre- and postpubertal females and males

Abstract Study question What is the gonadotoxicity of soft tissue sarcoma chemotherapies to better counsel females and males about the risk of infertility? Summary answer Limited data about the gonadotoxicity indicate a rather high risk with an average suspected infertility in females of 71% and in males of 54%. What is known already There is increasing awareness of the need to counsel young female and male cancer patients about the gonadotoxicity of chemotherapies and the risk of infertility. In addition, fertility preservation measures are offered in most countries. However, our knowledge of the gonadotoxicity of most cancer diseases and chemotherapies is still limited making it difficult to indicate fertility preservation measures. Soft tissue and mesothelial cancer are such a types of cancer for which data is very poor. The gonadotoxicity and risk of infertility of soft tissue and mesothelial cancer has not yet been systematically reviewed. Study design, size, duration This review is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search considering papers on gonadotoxicity of treatment of soft tissue sarcoma and mesothelial cancer was performed. A total of 2801 records were identified for abstract screening. The review was performed from December 2022 until October 2023. Participants/materials, setting, methods A literature search of papers published in the databases of MEDLINE, Embase, and Cochrane Library since 2000 was performed. Only females and males without metastases or recurrent disease were considered. Due to limited infertility data the outcome parameter “Suspected infertility” was defined based on reported low ovarian reserve parameters, low inhibin B, high gonadotropin concentration, gonadal dysfunction, amenorrhea, oligomenorrhea, azoospermia or oligozoospermia. Main results and the role of chance The database search yielded a total of 2801 abstracts, 136 of which were included in the full-text analysis. Of these, 7 studies, each on soft tissue sarcomas, could be included in the review. Studies on mesothelial cancer could not be identified. Two of the 7 soft tissue sarcoma studies were retrospective and 5 were prospective. Of the 7 studies, 3 provided data on women, 3 on men and 1 on both genders. A total of 28 women and 50 men, a total of 78, were included. The pubertal status could not be determined for all patients. Suspected infertility was found in 20 of 28 (71.4%, range 0-100%) of females (4 studies) and in 27 of 50 (54%, range 34.8-100%) of males (4 studies) soft tissue sarcoma patients. Limitations, reasons for caution The weakness is the inclusion of prepubertal and pubertal females and males, and the unknown pubertal status in some cases. A further weakness is the heterogenous spectrum of infertility markers and the limited number of studies which required to define for the analysis the rather vague outcome parameter “suspected infertility”. Wider implications of the findings Our data suggest a high risk of infertility due to chemotherapies in soft tissue sarcomas. This appears to be more pronounced in females than in males, although precise information cannot be given due to limited data. However, even though the study emphasizes the importance to consider fertility preservation measures. Trial registration number PROSPERO (Registry number CRD42023385402)

Estimating regional and national cancer incidence in Uganda: a retrospective population-based study, 2013–2017

BackgroundCancer is becoming a major health problem in Uganda. Cancer control requires accurate estimates of the cancer burden for planning and monitoring of the cancer control strategies. However, cancer estimates and trends for Uganda are mainly based on one population-based cancer registry (PBCR), located in Kampala, the capital city, due to a lack of PBCRs in other regions. This study aimed at estimating cancer incidence among the geographical regions and providing national estimates of cancer incidence in Uganda.MethodsA retrospective study, using a catchment population approach, was conducted from June 2019 to February 2020. The study registered all newly diagnosed cancer cases, in the period of 2013 to 2017, among three geographical regions: Central, Western and Eastern regions. Utilizing regions as strata, stratified random sampling was used to select the study populations. Cases were coded according to the International Classification of Diseases for Oncology (ICD-0-03). Data was analysed using CanReg5 and Microsoft Excel.Results11598 cases (5157 males and 6441 females) were recorded. The overall national age-standardized incidence rates (ASIR) were 82.9 and 87.4 per 100,000 people in males and females respectively. The regional ASIRs were: 125.4 per 100,000 in males and 134.6 per 100,000 in females in central region; 58.2 per 100,000 in males and 56.5 per 100,000 in females in Western region; and 46.5 per 100,000 in males and 53.7 per 100,000 in females in Eastern region. Overall, the most common cancers in males over the study period were cancers of the prostate, oesophagus, Kaposi’s sarcoma, stomach and liver. In females, the most frequent cancers were: cervix, breast, oesophagus, Kaposi’s sarcoma and stomach.ConclusionThe overall cancer incidence rates from this study are different from the documented national estimates for Uganda. This emphasises the need to enhance the current methodologies for describing the country’s cancer burden. Studies like this one are critical in enhancing the cancer surveillance system by estimating regional and national cancer incidence and allowing for the planning and monitoring of evidence-based cancer control strategies at all levels.

Suprapubic versus transurethral catheterization for bladder drainage in male rectal cancer surgery (GRECCAR10), a randomized clinical trial.

Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic catheterization (SPC), is still controversial. The aim was to compare the rates of urinary tract infection on the fourth postoperative day (POD4) between TUC and SPC, after rectal cancer surgery regardless of the day of removal of the urinary drain. This randomized clinical trial in 19 expert colorectal surgery centers in France and Belgium was performed between October 2016 and October 2019 and included 240 men (with normal or subnormal voiding function) undergoing mesorectal excision with low anastomosis for rectal cancer. Patients were followed at postoperative days4, 30, and 180. In 208 patients (median age 66years [IQR 58-71]) randomized to TUC (n = 99) or SPC (n = 109), the rate of urinary infection at POD4 was not significantly different whatever the type of drainage (11/99 (11.1%) vs. 8/109 (7.3%), 95%CI, - 4.2% to 11.7%; p = 0.35). There was significantly more pyuria in the TUC group (79/99 (79.0%) vs. (60/109 (60.9%), 95%CI, 5.7-30.0%; p = 0.004). No difference in bacteriuria was observed between the groups. Patients in the TUC group had a shorter duration of catheterization (median 4 [2-5] vs. 4 [3-5] days; p = 0.002). Drainage complications were more frequent in the SPC group at all followup visits. TUC should be preferred over SPC in male patients undergoing surgery for mid and/or lower rectal cancers, owing to the lower rate of complications and shorter duration of catheterization. ClinicalTrials.gov identifier NCT02922647.

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors: Antidiabetics Medications for Treating Diabetes

Type 2 diabetes (T2D) is a progressive disease, and most patients need to treat with monotherapy and combinations of oral hypoglycaemic drugs. At present about 500 million people worldwide are suffering from T2D. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption that result in glycosuria, modest weight loss and improve glycaemic control with a low risk of hypoglycaemia. These are used by T2D patients together with diet and exercise, either alone or in combination with other diabetes medicines. The main side-effects of SGLT-2 inhibitors are urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Some other probable adverse effects are lower limb amputations, risk of bone fractures, Fournier gangrene, male bladder cancer, female breast cancer, orthostatic hypotension, and acute kidney injury. This mini review explains aspects of SGLT-2 inhibitors with treatment procedures and side-effects.

Addressing disparities and enhancing accessibility in fertility preservation for male cancer patients in China.

Addressing disparities and enhancing accessibility in fertility preservation for male cancer patients in China.

Correlation of testosterone and ESR2 in prostate cancer

Introduction: Prostate cancer (PCa), as the second most frequent cancer in males, has a significant challenge in determining differential diagnosis and prognosis of aggressive or non-aggressive prostate cancer. For functioning correctly, the prostate needs sex steroid hormones, which are also factors in the initiation and progression of carcinogenesis. Risk and Gleason score upgrading can be predicted by preoperative plasma testosterone levels in men with prostate cancer undergoing radical prostatectomy. Not only testosterone but estrogen also has roles in prostate cancer carcinogenesis. Estrogen Receptor 2 (ESR2) gene has been found to encode ER-β, which has an anti-proliferative effect on prostate tissue. This study aims to look up any correlation between testosterone and ESR2 in prostate cancer. Methods: This is an analytic cross-sectional study. We conducted a quantitative real-time polymerase chain reaction (qPCR) examination involving 15 benign prostate hyperplasia (BPH), 10 non-metastasized PCa, and 21 PCa patients for determining ESR2 expression from formalin-fixed paraffin-embedded (FFPE) prostate cancer tissue with known testosterone level in our institution. Data were analyzed using statistical tests with a significance of p <0.05. Results: The mean testosterone level and ESR2 expression are 785 ng/dl and 236.4 ng/dl 4.6 8.2, respectively, in BPH and PCa. Statistically, there was an inverse correlation between testosterone and ESR2 levels in prostate cancer (p<0.05). Conclusion: This study found lower testosterone correlates with ESR2 modulation.

Odds of developing cancer among male and female volunteer firefighters in Florida: A case-control study design.

Determine whether volunteer firefighters in Florida are at increased odds of developing cancer compared to non-firefighters. A case-control study design was implemented to assess the odds of developing cancer among male and female volunteer firefighters in Florida. Gender-specific age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were estimated. Male volunteer firefighters were at increased odds for developing prostate (aOR = 1.26; 95%CI;[1.10- 1.44]) and male genital cancers combined (1.22;[1.07-1.39]), while reduced odds for endocrine cancer (0.41;[0.17-1.00]), and all leukemias (0.55;[0.35-0.86]), including lymphocytic (0.48;[0.24-0.97]); and chronic lymphocytic (0.40;[0.17-0.97]) leukemias. Female volunteer firefighters were at increased odds of developing of kidney cancer (2.51;[1.29-4.91]). Male volunteer firefighters are at increased odds for prostate and overall male genital cancers, while female volunteers are increased odds of kidney cancer.

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

Global status of research on fertility preservation in male patients with cancer: A bibliometric and visual analysis

BackgroundRecently, male fertility preservation before cancer treatment has become more prevalent. The research in this field has progressed over time, with some studies having a major impact and providing guidance for further research. However, the trends and hotspots of research on fertility preservation in male cancer patients may have changed; exploring them is essential for relevant research progress. DesignWe extracted relevant studies from the Web of Science Core Collection database, capturing information on the countries of study, affiliations, authors, keywords, as well as co-citations of references and journals. To identify publication trends, research strengths, key subjects, prominent topics, and emerging areas, we conducted a bibliometric analysis using CiteSpace. ResultsWe included 3201 articles on fertility preservation in male cancer patients published over January 1999 to December 2023 were included. Although the relevant research growth rate was slow initially, the number of publications increased annually. Of all study countries, the United States, Germany, and Japan reported the earliest studies; the United States published the highest number of relevant studies. The US institutions remained at the forefront for all 25 years, and the US researcher Ashok Agarwal published the most articles. Literature co-citation analyses indicated a transformation in the study participants; they comprised a younger demographic (i.e., a large number of adolescent male patients underwent fertility preservation); moreover, fertility preservation techniques evolved from sperm cryopreservation to testicular tissue cryopreservation. Research on reproductive outcomes of sperm cryopreservation was the recent hotspot in male fertility preservation research, and the impact of immunotherapy and checkpoint inhibitors on male fertility requires further research. ConclusionsMale fertility preservation will be a major future research focus, with closer connections and collaborations between countries and organizations. Our results present the historical data on the development of research on male fertility preservation in cancer patients, providing relevant insights for future research and development in this study area.

Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System.

Background and Objectives: Despite high incidences of cognitive impairment with aging, evidence on the prevalence and the seriousness of drug-induced cognitive impairment is limited. This study aims to evaluate the prevalence and the severity of drug-induced cognitive impairment and to investigate the clinical predictors of increased hospitalization risk from serious drug-induced cognitive impairment. Materials and Methods: Adverse drug events (ADEs) regarding drug-induced cognitive impairment reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were included (KIDS KAERS DB 2212A0073). The association between the etiologic classes and the reporting serious adverse events (SAEs) was evaluated using disproportionality analysis, and the effect was estimated with reporting odds ratio (ROR). Clinical predictors associated with increased risk of hospitalization from SAEs were identified via multivariate logistic analysis, and the effect was estimated with odds ratio (OR). Results: The most etiologic medication class for drug-induced cognitive impairment ADEs was analgesics, followed by sedative-hypnotics. Anticancer (ROR 57.105, 95% CI 15.174-214.909) and anti-Parkinson agents (ROR 4.057, 95% CI 1.121-14.688) were more likely to report serious drug-induced cognitive impairments. Male sex (OR 19.540, 95% CI 2.440-156.647) and cancer diagnosis (OR 18.115, 95% CI 3.246-101.101) are the major clinical predictors for increased risk of hospitalizations due to serious drug-induced cognitive impairment. Conclusions: This study highlights the significant prevalence and severity of drug-induced cognitive impairment with cancer diagnosis and anticancer agents. However, further large-scaled studies are required because of the potential underreporting of drug-induced cognitive impairments in real practice settings, which is further contributed to by the complexity of multiple contributing factors such as comorbidities.

Antiproliferative, apoptotic and anti-inflammatory potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues: Novel series of anticancer compounds

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.

Case-control study: Unveiling human polyomaviruses and papillomavirus in Egyptian colorectal cancer patients.

Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages. In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing. In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D. Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

Association of ankylosing spondylitis with the risk of cancer: a meta- analysis of cohort studies.

The potential impact of ankylosing spondylitis (AS) on cancer risk remains unclear. This study seeks to investigate the relationship between AS and different types of cancers. A literature search of the PubMed, Embase and Cochrane Library up to July 10th, 2023, was conducted. Two investigators selected eligible studies and extracted relevant data. The study used the random-effects model to explore the causality between AS and cancer, utilising relative risk (RR) as a measure for the study. A total of 20 cohorts with >330 000 participants were included. The pooling analysis shows AS being associated with a higher risk of cancers (RR = 1.16, 95% CI : 1.07-1.26, p= 0.001, I2=70.60%). In the subgroup analysis, AS has a higher cancer risk in Asia, but this association is not significant in Europe. Individual investigations indicate that AS is associated with an increased risk of bone cancer (RR = 3.41, 95% CI : 1.45-7.99, p= 0.005, I2=0.00%), thyroid gland cancer (RR = 1.76, 95% CI : 1.29-2.40, p< 0.001, I2=13.70%), multiple myeloma (RR = 1.74, 95% CI : 1.42-2.15, p< 0.001, I2=27.20%), leukaemia (RR = 1.52, 95% CI : 1.27-1.82, p< 0.001, I2=0.00%), kidney cancer (RR = 1.45, 95% CI : 1.08-1.94, p= 0.014, I2=0.00%), prostate cancer (RR = 1.43, 95% CI : 1.17-1.74, p< 0.001, I2=82.80%), and non-Hodgkin's lymphoma (RR = 1.42, 95% CI : 1.17-1.73, p< 0.001, I2=0.00%). However, there is no significant correlation with connective tissue cancer, brain cancer, testicular and other male cancers, bladder cancer, female cancers, skin cancer, and cancers of the digestive system and respiratory system. AS appears to be related to cancer development. The results highlighted the necessity for large-scale studies, considering influencing factors such as AS course, medication histories, and potential biases when examining cancer risk.

Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources.

Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account. Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex. A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes). Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future.

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Immune checkpoint inhibitor-related reproductive adverse effects: A pharmacovigilance analysis based on the FAERS database.

e14707 Background: There exists a critical need to systematically understand the extent and magnitude of immune checkpoint inhibitor (ICI)-related reproductive adverse effects, which may not only pose long-term implications for patients who may desire future fertility, but also impact the quality of life. We aim to better understand this underexplored area. Methods: Our focus was on ICIs approved by the FDA as of June 31, 2023, including anti-PD-1 agents (nivolumab, pembrolizumab, cemiplimab, dostarlimab, retifanlimab), anti-PD-L1 agents (atezolizumab, avelumab, durvalumab), anti-CTLA-4 agents (ipilimumab, tremelimumab), and an anti-LAG-3 agent (relatlimab). We analyzed 13,702,373 cases from January 1, 2015, to June 30, 2023. We included adverse reactions under the 'Reproductive system and breast disorders' category in the SOC (System Organ Classes). For signal detection, we used the reporting odds ratio (ROR) method. Results: We identified 133,512 patients administered with ICIs, among whom 568 reported irRAEs. Abnormal spermatogenesis (ROR025: 7.91), scrotal irritation (ROR025: 3.83), scrotal oedema (ROR025: 1.90), perineal rash (ROR025: 1.38), prostatitis (ROR025: 1.25), acquired phimosis (ROR025: 1.20), and scrotal erythema (ROR025: 1.08) in males and genital tract fistula in females (ROR025: 2.72) were detected as significant irRAEs. Among them, the most commonly reported irRAEs were prostatitis (n=29), scrotal oedema (n=12), and abnormal spermatogenesis (n=6) in males and genital tract fistula (n=34) in females. Male patients had a lower risk compared to females (OR=0.68 [0.57-0.81], p&lt;0.0001). There was no marked difference between the patients on polytherapy vs. monotherapy (OR=0.90 [0.71-1.13], p=0.36). PD-1 inhibitors pose the greatest risk when compared with CTLA-4 inhibitors (OR=1.65 [1.05-2.79], p=0.045). Gynecologic cancers in females (OR=3.77 [2.82-4.99], p&lt;0.0001) and urogenital cancers in males (OR=1.56 [1.17-2.06], p=0.0018) were strong risk factors. Additional targeted therapy, particularly lenvatinib (OR=3.79 [2.71-5.15], p&lt;0.0001) and cabozantinib (OR=2.69 [1.66-4.09], p&lt;0.0001) significantly increased the risk (OR=1.87 [1.52-2.29], p&lt;0.0001) and this risk appeared to be more pronounced in females (OR=2.32 [1.76-3.02], p&lt;0.0001). Additional chemotherapy was associated with a significantly reduced risk in males (OR=0.65 [0.42-0.96], p=0.042). However, doxorubicin (OR=2.58 [1.10-5.05], p=0.013) and cyclophosphamide (OR=2.36 [0.93-4.83], p=0.038) were linked to an elevated risk. Conclusions: Our findings demonstrated that ICIs could lead to a wide range of irRAEs in both males and females. Additional therapies could change the risk of irRAEs. Despite the current lack of high-quality clinical data on this topic, it is reasonable to inform patients about the plausible risk of irRAEs.