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Scientific Reports Jan 2024Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the...
Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis.
Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats' testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation.
Topics: Humans; Male; Rats; Animals; Cisplatin; Etoposide; Testicular Neoplasms; Bleomycin; Antioxidants; Alginates; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53; bcl-2-Associated X Protein; Antineoplastic Combined Chemotherapy Protocols; Semen; Testosterone; Oxidative Stress; Apoptosis; Inflammation
PubMed: 38238398
DOI: 10.1038/s41598-024-52010-w -
South Asian Journal of Cancer Apr 2021Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be...
Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be salvaged with systemic therapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Complete remission can be obtained in approximately 50 to 60% of patients treated with HDCT. Our experience reports the efficacy and safety of HDCT followed by ASCT in relapsed GCT. Analysis of patient records (2012-2019) showed that three patients had received HDCT and ASCT. All the three patients were treated with BEP (bleomycin, etoposide, and cisplatin) as first-line therapy. HDCT was done in Case 1 after third-line salvage and in other two patients after second-line salvage chemotherapies. High-dose carboplatin and etoposide were used as conditioning regimen. Granulocyte colony-stimulating factor was used for the mobilization of stem cells. After ASCT, complete remission was documented in all the patients. All were alive and disease-free till the last follow-up. Grade ¾ toxicities including myelosuppression, diarrhea, and mucositis were observed in all three patients. This is the first report from India on HDCT with ASCT in GCT. HDCT/ASCT seems to be feasible, safe, and effective in relapsed testicular GCTs.
PubMed: 34568223
DOI: 10.1055/s-0041-1731516 -
European Journal of Psychotraumatology 2021: Traumatic events can be related to severe transgressions or violations of moral boundaries. Moral injury (MI) has been described as 'the lasting psychological,...
: Traumatic events can be related to severe transgressions or violations of moral boundaries. Moral injury (MI) has been described as 'the lasting psychological, biological, spiritual, behavioral and social impact of perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations.' These events can provoke emotions such as remorse, guilt and shame, and affects someone's self-image and identity. : The aim of the study is to evaluate a treatment protocol that addresses the specific characteristics of moral trauma in treatment of PTSD, next to anxiety. : Brief Eclectic Psychotherapy for Moral Trauma (BEP-MT) is an adaptation of the evidence-based Brief Eclectic Psychotherapy for PTSD (BEPP). BEP-MT integrates components of cognitive-behavioural, psychodynamic, constructivist, and systemic psychotherapy. In the current study treatment progress of a refugee Dusan was monitored. Prior to and after treatment the Clinical-Administered PTSD Scale for DSM-5, the PTSD Checklist (PCL-5), the Brief Symptom Inventory (BSI) and the Moral Injury Appraisal Scale (MIAS) were administered. Every session moral emotions were assessed on a Likert scale. : Whereas PTSD complaints and strong feelings of guilt and shame were manifest prior to treatment, during BEP MT a gradual decline in the intensity of the moral emotions was found. After BEP-MT Dusan no longer met criteria for PTSD and his psychological complaints diminished. : The case of Dusan has shown it is worthwhile to address moral trauma and BEP- MT is a promising treatment protocol for patients suffering from PTSD after moral trauma. Further research is needed to examine the effectiveness of BEP-MT.
Topics: Adult; Anxiety; Clinical Protocols; Emotions; Guilt; Humans; Male; Netherlands; Psychotherapy; Refugees; Self Concept; Stress Disorders, Post-Traumatic; Surveys and Questionnaires
PubMed: 34262665
DOI: 10.1080/20008198.2021.1929026 -
European Urology Open Science Nov 2021Germ cell tumors represent highly curable disease even in metastatic stage. However, poor-risk patients with an unfavorable serum tumor marker (STM) decline after the...
Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial.
BACKGROUND
Germ cell tumors represent highly curable disease even in metastatic stage. However, poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP).
OBJECTIVE
The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population.
DESIGN SETTING AND PARTICIPANTS
This was an open-labeled, nonrandomized, single-center phase II trial to study the efficacy and toxicity of TIP in the first-line treatment of germ cell tumor patients with an unfavorable decline of STMs. Nineteen patients with a poor prognosis according to the International Germ Cell Cancer Collaboration Group classification and an unfavorable STM decline after the first cycle of chemotherapy were included in this phase II study (NCT02414685). The treatment regimen consisted of paclitaxel 250 mg/m on day 1, ifosfamide 1200 mg/m on days 1-5, and cisplatin 20 mg/m on days 1-5, totally for four cycles.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary endpoint was complete response (CR) rate. An optimal Simon two-stage design was used with a type I error of 5% and study power of 80%. If fewer than six CRs to study therapy have been observed among the first 19 patients, the study was to be terminated.
RESULTS AND LIMITATIONS
A CR was achieved in four (21.1%) patients; therefore, the study was terminated in the first stage. A favorable response rate (CR or partial remission with negative tumor markers) was observed in 14 (78.9%) patients. At a median follow-up period of 35.2 mo (range, 5.6-62.1 mo), ten (52.6%) patients experienced disease progression and eight patients (42.1%) died. The 2-yr progression-free and overall survival was 41.2% (95% confidence interval [CI] 16.8-65.7) and 72.7% (95% CI 48.9-96.4), respectively. TIP was well tolerated, and no unexpected toxicity was observed. No informative biomarkers, including miR-371a-3p was identified.
CONCLUSIONS
Treatment modification from the BEP to the TIP regimen in patients with an unfavorable STM decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population.
PATIENT SUMMARY
Poor-risk patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with an approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Treatment modification from the BEP regimen to the paclitaxel, ifosfamide, and cisplatin regimen in patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population.
PubMed: 34738090
DOI: 10.1016/j.euros.2021.09.002 -
Frontiers in Oncology 2022Extragonadal yolk sac tumor (YST) of peritoneum is a rare malignancy.
BACKGROUND
Extragonadal yolk sac tumor (YST) of peritoneum is a rare malignancy.
CASE DESCRIPTION
A 37-year-old Chinese woman was admitted to hospital with a 3-month abdominal pain 4 years ago. Alpha-fetoprotein was 228,499.0 ng/mL. Computed tomography scan revealed a massive mass in the left lower abdomen. Exploratory laparotomy exposed a huge mesenteric mass. Then, mesenteric tumor resection, partial sigmoidectomy, and single-lumen fistula of sigmoid colon were performed. Postoperative pathologic diagnosis reported a stage IV mesenteric YST. After surgery, the patient received 6 courses of BEP (bleomycin, etoposide, and cisplatin) chemotherapy. Seven months later, the patient underwent stoma reversion of sigmoid colon and received another 2 courses of BEP chemotherapy. Three months after the last chemotherapy, liver metastases were diagnosed. She subsequently underwent 3 surgeries, radiotherapy for liver metastases, and multiple tiers of palliative chemotherapies, including TP (docetaxel and carboplatin), VIP (ifosfamide, cisplatin, and etoposide), TIP (paclitaxel, ifosfamide, and cisplatin), and so on. After the third surgery (left hepatic lesion resection and right iliac lymph node resection), she received 4 cyclic chemotherapies of BEP´ (boanmycin, etoposide, and cisplatin) without pulmonary toxic side effects.
CONCLUSION
Postoperative histopathology and immunohistochemistry are gold standards for the diagnosis of peritoneal YST. The standard first-line treatment is surgery plus BEP chemotherapy. Second-line therapy regimens and above, including VIP and TIP, improve the prognosis of recurrent germ cell tumors. This relapsed and refractory patient with peritoneal YST benefits from the secondary BEP´ chemotherapy.
PubMed: 36016622
DOI: 10.3389/fonc.2022.928234 -
Journal of Ovarian Research Apr 2021Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought... (Review)
Review
BACKGROUND
Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis.
CASE PRESENTATION
A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma.
CONCLUSION
Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.
Topics: Adult; Choriocarcinoma; Female; Humans; Neoplasm Metastasis; Ovarian Neoplasms; Prognosis
PubMed: 33888146
DOI: 10.1186/s13048-021-00810-3 -
Biomedicine & Pharmacotherapy =... Jun 2021There is growing concern that some cytotoxic regimens for cancer adversely affect spermatogenesis and male fertility. Increasing evidence demonstrated that melatonin has...
There is growing concern that some cytotoxic regimens for cancer adversely affect spermatogenesis and male fertility. Increasing evidence demonstrated that melatonin has beneficial impacts on reproductive processes; however, whether melatonin can protect against bleomycin, etoposide, and cisplatin (BEP) chemotherapy regimen-induced testicular toxicity, remains obscure. The present study aimed to explore the effect of melatonin on BEP-evoked testicular injury in rats. Adult male Wistar rats (n = 10/group) were intraperitoneally (i.p.) injected with one cycle of 21 days of 0.33 therapeutically relevant dose levels of BEP (.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin) with or without melatonin. At the end of the study, sperm parameters, testosterone level, stereology of testes, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), the expression of apoptosis-associated genes such as Bcl2, Bax, Caspase-3, p53, and TNF-α (Real-time PCR and Immunohistochemistry) were evaluated. Our findings showed that melatonin restored spermatogenesis by improving sperm count, motility, viability, and morphology. Testosterone level, histopathology, and stereology of testes were significantly improved in melatonin-administrated groups. Furthermore, melatonin recovered the oxidative status of the testes through elevating TAC and ameliorating MDA and NO levels. More importantly, melatonin therapy suppressed BEP-evoked apoptosis by modulating Bcl-2, Bax, Caspase-3, p53, and TNF-α expression in testes. In conclusion, melatonin protects the testes against BEP-induced testicular damage by attenuating nitro-oxidative stress, apoptosis, and inflammation, which provides evidence for melatonin as a possible clinical therapy against BEP-associated gonadotoxicity and male sub/infertility.
Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Bleomycin; Cisplatin; Cytoprotection; Dose-Response Relationship, Drug; Etoposide; Male; Melatonin; Oxidative Stress; Rats; Rats, Wistar; Testis
PubMed: 33752059
DOI: 10.1016/j.biopha.2021.111481 -
BMJ Open Mar 2021Adequate nutrition during pregnancy is crucial to both mother and child. Maternal malnutrition can be the cause of stillbirth or lead to poor birth outcomes such as...
Effect of balanced energy-protein supplementation during pregnancy and lactation on birth outcomes and infant growth in rural Burkina Faso: study protocol for a randomised controlled trial.
INTRODUCTION
Adequate nutrition during pregnancy is crucial to both mother and child. Maternal malnutrition can be the cause of stillbirth or lead to poor birth outcomes such as preterm delivery and small-for-gestational-age newborns. There is a probable positive effect of providing pregnant women a balanced energy-protein (BEP) food supplement, but more evidence is needed. The MIcronutriments pour la SAnté de la Mère et de l'Enfant (MISAME) III project aims to improve birth outcomes and infant growth by testing a BEP supplement during pregnancy and lactation in rural Burkina Faso. This paper describes the study protocol.
METHODS AND ANALYSIS
MISAME-III is a four-arm individually randomised efficacy trial implemented in six rural health centre catchments areas in the district of Houndé. Eligible pregnant women, aged between 15 and 40 years old and living in the study areas, will be enrolled. Women will be randomly assigned to one of the four study groups: (1) prenatal intervention only, (2) postnatal intervention only, (3) prenatal and postnatal intervention or (4) no prenatal or postnatal intervention. The intervention group will receive the BEP supplement and iron/folic acid (IFA) tablets, while the control group will only receive the IFA tablets following the national health protocol. Consumption will be supervised by trained village women on a daily basis by means of home visits. The primary outcomes are small-for-gestational age at birth and length-for-age z-score at 6 months of age. Secondary outcomes will be measured at birth and during the first 6 months of the infants' life. Women will be enrolled from October 2019 until the total sample size is reached.
ETHICS AND DISSEMINATION
MISAME-III has been reviewed and approved by the University Hospital of Ghent and the ethics committee of Centre Muraz, Burkina Faso. Informed consent will be obtained. Results will be published in relevant journals and shared with other researchers and public health institutions.
TRIAL REGISTRATION NUMBER
NCT03533712.
Topics: Adolescent; Adult; Breast Feeding; Burkina Faso; Child; Child, Preschool; Dietary Supplements; Female; Folic Acid; Humans; Infant; Infant, Newborn; Lactation; Pregnancy; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33762226
DOI: 10.1136/bmjopen-2020-038393 -
Cancers Nov 2023The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant...
OBJECTIVE
The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options.
METHODS
The clinical data of children with extracranial GCTs in three children's medical centers in Shanghai were retrospectively analyzed.
RESULTS
In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors ( < 0.0.0001, χ = 23.6638, = 0.0225, χ = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) ( < 0.05).
CONCLUSIONS
The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.
PubMed: 38001671
DOI: 10.3390/cancers15225412 -
Journal of Clinical Oncology : Official... Apr 2020Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little...
PURPOSE
Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.
PATIENTS AND METHODS
Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.
RESULTS
Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.
CONCLUSION
Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemotherapy, Adjuvant; Cisplatin; Etoposide; Humans; Male; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Progression-Free Survival; Retrospective Studies; Survival Rate; Testicular Neoplasms; Treatment Outcome
PubMed: 31877087
DOI: 10.1200/JCO.19.01876