Advances in diagnosis and treatment of testicular cancer

Chovanec, Michal; Cheng, Liang

doi:10.1136/bmj-2022-070499

Cited by 37 publications

(37 citation statements)

References 179 publications

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“…Underlying molecular pathways of late cognitive impairment in GCTs are unknown. GCT survivors constitute a unique population of men cured from GCT with multimodal approach using chemotherapy, radiotherapy and surgery ( 21 ). In our prospective translational study, we have examined a set of GMT biomarkers as potential biomarkers of cognitive impairment in long-term survivors of GCTs.…”

Section: Discussionmentioning

confidence: 99%

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

et al. 2023

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BackgroundSurvivors of testicular germ cell tumors (GCT) may suffer from late cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis.MethodsGCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial translocation and dysbiosis high mobility group box-1 (HMGB-1), lipopolysaccharide, d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6).ResultsGCT survivors with higher sCD14 (above median) had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overall cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and lipopolysaccharide. Survivors treated with ≥ 400mg/m2 vs < 400mg/m2 of cisplatin-based chemotherapy had a higher lipopolysaccharide (567.8 μg/L ± 42.7 vs 462.9 μg/L ± 51.9, (p = 0.03).ConclusionssCD14 is a marker of monocytic activation by lipopolysaccharide and may also serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors within the gut-brain axis.

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Section: Discussionmentioning

confidence: 99%

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

et al. 2023

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“…Searching for isochromosome 12p for identification of germ cell tumors (GCTs) is the only molecular genetic tool employed in selected cases of testis tumors (Wyvekens et al 2022 ). Histology forms the basis for the first strategic decision in the management of testicular neoplasms, because benign tumors do not need further treatment after surgery while the management of GCTs needs to be tailored to seminomatous or nonseminomatous histology and secondly to clinical stage (Cheng et al 2018 ; Chovanec and Cheng 2022 ). Elevation of traditional serum tumor markers alpha fetoprotein (AFP), beta human chorionic gonadotropin (bHCG) and lactate dehydrogenase (LDH) is a typical feature of nonseminomatous GCTs, while it is less frequently found in seminomas and it is not observed in other testicular neoplasms (Leão et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Testicular neoplasms: the interrelationships of serum levels of microRNA-371a-3p (M371) and classical tumor markers with histology, clinical staging, and age—a statistical analysis

Dieckmann

Dumlupinar

Grobelny

et al. 2023

J Cancer Res Clin Oncol

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Purpose In testicular neoplasms, the interrelationship of elevations of the novel serum tumor marker microRNA-371a-3p (M371) and traditional markers with other clinical features is still incompletely understood. The present study evaluated marker expression rates in relation to various other clinical parameters. Methods The following data were retrospectively registered from 641 consecutive patients with testicular neoplasms: histology, such as seminoma (n = 365), nonseminoma (n = 179), benign tumor (n = 79), other malignant tumor (n = 18); patients age (years); clinical stage (CS1, CS2a/b, CS2c, CS3); and preoperative elevation of beta HCG, AFP, LDH, M371 (yes/no). Descriptive statistical methods were employed with comparisons of various subgroups to disclose associations of marker expression rates with age, histology and CS, and of age with histology. Results The histologic subgroups revealed significantly different expression rates of tumor markers. M371 performed best with expression rates of 82.69% and 93.58% in seminoma and in nonseminoma, respectively. In germ cell tumors, all markers had significantly higher expression rates in metastasized stages than in localized disease. All markers except LDH have significantly higher expression rates in younger than in older patients. Nonseminoma is most prevalent in the youngest age category, seminoma predominates in patients > 40 years, other malignancies were restricted to patients > 50 years. Conclusion The study documented significant associations of serum marker expression rates with histology, age and clinical staging, with highest rates in nonseminomas, young age and advanced clinical stages. M371 showed significantly higher expression rates than other markers suggesting its superior clinical usefulness.

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“…Testicular cancer (TC) is the most common malignancy in young men, with an increasing incidence over the past 30 years (1,2). It affects males during the peak of reproductive life and causes a decline in male reproductive health which is associated with reduced semen quality, increased germ cell abnormalities, and infertility (1,3).…”

Section: Introductionmentioning

confidence: 99%

Loss of liver kinase B1 in human seminoma

Kumar

Sahoo²,

Jamaluddin³

et al. 2023

Front. Oncol.

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Testicular cancer is a common malignancy of young males and is believed to be originated from defective embryonic or adult germ cells. Liver kinase B1 (LKB1) is a serine/threonine kinase and a tumor suppressor gene. LKB1 is a negative regulator of the mammalian target of rapamycin (mTOR) pathway, often inactivated in many human cancer types. In this study, we investigated the involvement of LKB1 in the pathogenesis of testicular germ cell cancer. We performed immunodetection of LKB1 protein in human seminoma samples. A 3D culture model of human seminoma was developed from TCam-2 cells, and two mTOR inhibitors were tested for their efficacy against these cancer cells. Western blot and mTOR protein arrays were used to show that these inhibitors specifically target the mTOR pathway. Examination of LKB1 showed reduced expression in germ cell neoplasia in situ lesions and seminoma compared to adjacent normal-appearing seminiferous tubules where the expression of this protein was present in the majority of germ cell types. We developed a 3D culture model of seminoma using TCam-2 cells, which also showed reduced levels of LKB1 protein. Treatment of TCam-2 cells in 3D with two well-known mTOR inhibitors resulted in reduced proliferation and survival of TCam-2 cells. Overall, our results support that downregulation or loss of LKB1 marks the early stages of the pathogenesis of seminoma, and the suppression of downstream signaling to LKB1 might be an effective therapeutic strategy against this cancer type.

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Advances in diagnosis and treatment of testicular cancer

Cited by 37 publications

References 179 publications

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

Testicular neoplasms: the interrelationships of serum levels of microRNA-371a-3p (M371) and classical tumor markers with histology, clinical staging, and age—a statistical analysis

Loss of liver kinase B1 in human seminoma

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