A pioneering study of the radiological mapping in the world's largest mangrove forest (the Sundarbans) and implications for the public and environment.

Coastal Mangroves are facing growing threats due to the harmful consequences of human activities. This first-ever detailed study of natural radioactivity in soil samples collected from seven tourist destinations within the Sundarbans, the world's largest mangrove forest, was conducted using HPGe gamma-ray spectrometry. Although the activity levels of 226Ra (11 ± 1-44 ± 4 Bq/kg) and 232Th (13 ± 1-68 ± 6 Bq/kg) generally align with global averages, the concentration of 40K (250 ± 20-630 ± 55 Bq/kg) was observed to surpass the worldwide average primarily due to factors like salinity intrusion, fertilizer application, agricultural runoff, which suggests the potential existence of potassium-rich mineral resources near the study sites. The assessment of the hazard parameters indicates that the majority of these parameters are within the recommended limits. The soil samples do not pose a significant radiological risk to the nearby population. The results of this study can establish important radiological baseline data before the Rooppur Nuclear Power Plant begins operating in Bangladesh.

Measurement of radioactivity in soils of Karamjal and Harbaria mangrove forest of Sundarbans for establishment of radiological database.

This work presents the first in-depth study of soil radioactivity in the mangrove forest of Bangladesh part of the Sundarbans. It used HPGe gamma-ray spectrometry to measure the amount of natural radioactivity in soil samples from Karamjal and Harbaria sites of the world's largest mangrove forest. The activity concentrations of most of the 226Ra (14±2 Bqkg-1 to 35±4 Bqkg-1) and 232Th (30±5 Bqkg-1 to 50±9 Bqkg-1) lie within the world average values, but the 40K concentration (370± 44 Bqkg-1 to 660±72 Bqkg-1) was found to have exceeded the world average value. The evaluation of radiological hazard parameters revealed that the outdoor absorbed dose rate (maximum 73.25 nGyh-1) and outdoor annual effective dose (maximum 0.09 mSvy-1) for most samples exceeded the corresponding world average values. The elevated concentration of 40K is mainly due to the salinity intrusion, usage of fertilizers and agricultural runoff, and migration of waste effluents along the riverbanks. Being the pioneering comprehensive research on the Bangladesh side of the Sundarbans, this study forms a baseline radioactivity for the Sundarbans before the commissioning of the Rooppur Nuclear Power Plant in Bangladesh.

Evaluation of radioactivity in soil and rock samples from an undiscovered sea beach in the southeastern coastline of Bangladesh and associated health risk.

This study marks the first-ever assessment of radiological hazards linked to the sands and rocks of Patuartek Sea Beach, situated along one of the world's longest sea beaches in Cox' Bazar of Bangladesh. Through the utilization of an HPGe detector, a comprehensive analysis of the activity concentrations of 226Ra, 232Th, and 40 K was conducted, and their activity ranged from 7 to 23 Bq/kg, 9-58 Bq/kg, and 172-340 Bq/kg, respectively, in soils, and 19-24 Bq/kg, 27-39 Bq/kg, and 340-410 Bq/kg, respectively, in rocks. Some sand samples exhibited elevated levels of 232Th, while the rock samples displayed higher levels of 40 K compared to the global average. The radiological hazard parameters were assessed, and no values surpassed the recommended limits set by several international organizations. Hence, the sands and rocks of Patuartek sea beach pose no significant radiological risk to the residents or tourists. The findings of this study provide crucial insights for the development of a radiological baseline map in the country, which is important due to the commissioning of the country's first nuclear power plant Rooppur Nuclear Power Plant. The data may also stimulate interest in the rare-earth minerals present in the area, which is important for the electronics industry, thorium-based nuclear fuel cycles.

Evaluation of transfer factors of 226Ra, 232Th, and 40K radionuclides from soil to grass and mango in the northern region of Bangladesh.

Bangladesh is a rapidly developing country, which is vulnerable to various types of pollution due to the large-scale industrial and associated human activities that might potentially affect the locally harvested foodstuffs. Therefore, the transfer factor is an essential tool to assess the safety of foodstuffs due to the presence of natural radioactivity in environmental matrix and/or strata. This is a first study of its kind conducted in a well-known region for mango farming in Bangladesh, measuring the uptake of naturally occurring radioactive materials (NORMs) by grass and mango from soil to assess the ingestion doses to humans. The HPGe gamma-ray detector was used to determine the concentrations of NORMs in samples of soil (20), grass (10), and mango (10), which were then used to calculate the transfer factors of soil to grass and soil to mango. Average activity concentrations of 226Ra, 232Th, and 40K in associated soil samples (47.27 ± 4.10, 64.49 ± 4.32, 421.60 ± 28.85) of mango and 226Ra and 232Th in associated soil samples (45.07 ± 3.93, 52.17 ± 3.95) of grass were found to exceed the world average values. The average transfer factors (TFs) for mango were obtained in the order of 40K(0.80) > 226Ra (0.61) > 232Th (0.31), and for grass, it shows the order of 40K (0.78) > 232Th (0.64) > 226Ra (0.56). However, a few values (3 mango samples and 3 grass samples) of the estimated TFs exceeded the recommended limits. Moreover, Bangladesh lacks the transfer factors for most of the food crops; therefore, calculation of TFs in the major agricultural products is required all over Bangladesh, especially the foodstuffs produced near the Rooppur Nuclear Power Plant, which is scheduled to be commissioned in 2023.

Vertical distributions of radionuclides along the tourist-attractive Marayon Tong Hill in the Bandarban district of Bangladesh.

This is the first attempt in the world to depict the vertical distribution of radionuclides in the soil samples along several heights (900 feet, 1550 feet, and 1650 feet) of Marayon Tong hill in the Chittagong Hill Tracts, Bandarban by HPGe gamma-ray spectrometry. The average activity concentrations of 232Th, 226Ra, and 40K were found to be 37.15 ± 3.76 Bqkg-1, 19.69 ± 2.15 Bqkg-1, and 347.82 ± 24.50 Bqkg-1, respectively, where in most cases, 232Th exceeded the world average value of 30 Bqkg-1. According to soil characterization, soils ranged from slightly acidic to moderately acidic, with low soluble salts. The radium equivalent activity, outdoor and indoor absorbed dose rate, external and internal hazard indices, external and internal effective dose rates, gamma level index, and excess lifetime cancer risk were evaluated and found to be below the recommended or world average values; but a measurable activity of 137Cs was found at soils collected from ground level and at an altitude of 1550 feet, which possibly arises from the nuclear fallout. The evaluation of cumulative radiation doses to the inhabitants via periodic measurement is recommended due to the elevated levels of 232Th.This pioneering work in mapping the vertical distribution of naturally occurring radioactive materials (NORMs) can be an essential factual baseline data for the scientific community that may be used to evaluate the variation in NORMs in the future, especially after the commissioning of the Rooppur Nuclear Power Plant in Bangladesh in 2024.

Clinico-epidemiological Characteristics of Asymptomatic and Symptomatic COVID-19-Positive Patients in Bangladesh.

As of August 15, 2020, Bangladesh lost 3591 lives since the first Coronavirus disease 2019 (COVID-19) case announced on March 8. The objective of the study was to report the clinical manifestation of both symptomatic and asymptomatic COVID-19-positive patients. An online-based cross-sectional survey was conducted for initial recruitment of participants with subsequent telephone interview by the three trained physicians in 237 adults with confirmed COVID-19 infection in Bangladesh. The study period was 27 April to 26th May 2020. Consent was ensured before commencing the interview. Collected data were entered in a pre-designed case record form and subsequently analyzed by SPSS 20.0. The mean±SD age at presentation was 41.59±13.73 years and most of the cases were male (73.0%). A total of 90.29% of patients reside in urban areas. Among the positive cases, 13.1% (n=31) were asymptomatic. Asymptomatic cases were significantly more common in households with 2 to 4 members (p=0.008). Both symptomatic and asymptomatic patients shared similar ages of presentation (p=0.23), gender differences (p=0.30) and co-morbidities (p=0.11). Only 5.3% of patients received ICU care during their treatment. The most frequent presentation was fever (88.3%), followed by cough (69.9%), chest pain (34.5%), body ache (31.1%), and sore throat (30.1%). Thirty-nine percent (n=92) of the patients had co-morbidities, with diabetes and hypertension being the most frequently observed. There has been an upsurge in COVID-19 cases in Bangladesh. Patients were mostly middle-aged and male. Typical presentations were fever and cough. Maintenance of social distancing and increased testing are required to meet the current public health challenge.

Pattern of Initial Clinical Presentation of Systemic Lupus Erythematosus: A Hospital-Based Cross-Sectional Study from Bangladesh.

Systemic lupus erythematosus (SLE) is an autoimmune disorder involving multiple systems and often presents with diverse clinical manifestations. The objective of the present study was to investigate the initial clinical presentations of SLE patients attending a tertiary care hospital in Bangladesh. This cross-sectional study was conducted among 85 SLE patients diagnosed according to the 1997 ACR Revised Criteria for Classification of SLE attending the Lupus Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2012 to June 2013. Sociodemographic and clinical data were collected from patient interviews, physical examinations and medical records. Almost 75.0% of the patients aged below 30 years had a female predominance (male-female ratio 1:5.6). Fever (71.0%), joint pain (60.0%) and alopecia (28.0%) were the most common initial presentations among the patients. Constitutional symptoms such as fatigue, malaise and weakness (23.5%), malar rash (21.0%), oral ulcer (20.0%), photosensitivity (15.0%) and Raynaud's phenomenon (13.0%) were also present in variable proportions. The musculoskeletal and mucocutaneous systems were most commonly affected (85.0% and 75.0% respectively), followed by lupus nephritis (40.0%), hematological symptoms (22.0%) and vasculitis (17.6%). Out of 85 patients, 78 (92.0%) tested positive for anti-nuclear antibodies. SLE patients commonly present with musculoskeletal and nonspecific symptoms at the initial phase. Hence, physicians should consider this clinical and immunological evidence along with conventional symptoms included in the ACR criteria.

Proportion and Pattern of Central Nervous System Involvement in Acute Leukemia on Diagnosis.

The most common malignant neoplasm in Childhood is Leukemia which is about 41% of all malignancies. Incidence of CNS involvement is less than 5% in Acute Lymphoblastic Leukemia and 6-29% in Acute Myeloblastic Leukemia at Diagnosis. For Successful treatment of childhood leukemia it is mandatory, to give sufficient therapy directed to the CNS to treat sub clinical or overt CNS Leukemia. Without Central Nervous System- Directed therapy, relapses originating from the CNS in up to 75% cases. For this purpose it is crucial to find out the CNS involvement in acute leukemia at diagnosis. This study was conducted to find proportion and pattern of central nervous system involvement (central nervous system manifestation and/or cerebrospinal fluid findings) in acute leukemia at diagnosis in Bangladesh. A cross sectional study was conducted from May 2012 to November 2012 in the Department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Total 50 samples were included those having age <15 years newly diagnosed with acute leukemia by purposive sampling. Common age group 1-5 years (48%), 32 patients (64%) were male and 18 patients (36%) were female. Out of 32 male patients 4 patients presented with CNS manifestation and among 18 female patients 2 patients presented with CNS manifestation. There is no association between sex and CNS presentation (P value 0.89). 25 (50%) patients had total leukocyte count >11,000-1,00,000. Twelve (24%) patients had total leukocyte count <4,000. Eight (16%) patients had total leukocyte count 4,000-11,000, and rest 05(10%) patients had leukocyte count >1,00,000. Proportion of CNS manifestation was found 6/50 patients. Eight (8) patients were suffering from AML and 42 patients were suffering form ALL. Among 8 AML patients 1 (11.1%) patient had CNS manifestation and Among 42 ALL patients 5(11.1%) patients had CNS manifestation. Out of 6 patients with CNS manifestation, 2 (04%) patients presented with clinical manifestation, and 5(10%) had positive CSF findings. Pattern of CSF finding of 50 leukemic children CNS-1 90%, CNS-2 02%, CNS-3 08%, and no patients had traumatic lumber puncture with concomitant presence of blasts cells. There is significant association was found between hyper leukocytosis and CNS manifestation (p=0.138) but there is no statistically significant association between positive CSF findings and neurological findings (p=0.082). At conclusion, CNS manifestation is not uncommon (6/50 patients) was found in acute leukemia at diagnosis. So, every patient of acute leukemia should be examined carefully for CNS involvement along with CSF cytospin.

Association of Modified Sequential Organ Failure Assessment (MSOFA) Score and C-reactive protein (CRP) With the Outcome of Patients under Mechanical Ventilation.

Different scoring systems has been discovered in medical practice, more specifically for ICU treatment, are designed to objectively quantify physiologic derangements and comorbid conditions for estimating mortality, length of stay and ICU resource use. This observational and descriptive study was carried out in the ICU, BSMMU, Dhaka, during March 2014 to May 2016, to determine the association of MSOFA score, CRP level with the outcome of patients on mechanical ventilation as well as compare the MSOFA and CRP combined with MSOFA alone. For this purpose, a total of 60 critically ill patients admitted in the above hospital were included in this study. Patients with an ICU stay of less than 48 hours, readmissions not considered, known case of neuromuscular disease, connective tissue disorder, renal disease and pregnancy and Patients refused to give written consent were excluded from the study. Patients who had MSOFA ≥7, their mean duration of ICU stay were 10.9±6.7 days and mean duration of mechanical ventilation 7.63±5.2 days. Patients who had CRP >11mg/L, their mean duration of ICU stay was 10.8±7.2 days and mean duration of mechanical ventilation was 7.35±5.1 days. Patients who had MSOFA score ≥7 and CRP ≥11mg/L with mean duration of ICU stay was 10.82±7.2 days and mean duration of mechanical ventilation was 7.12±5.2 days. 69.2% patients were CRP status positive (≥11) in death group and 33.3% had alive group. 92.3% patients were Positive (CRP ≥7 or MSOFA ≥11) in death group and 14.3% had alive group. MSOFA identified true positive 32 cases for death, false positive 5 cases, false negative 7 cases and true negative 16 cases confirmed by patient's outcome. CRP level identified true positive 27 cases for death, false positive 7 cases, false negative 12 cases and true negative 14 cases confirmed by patients outcome. Combined (CRP ≥11mg/L and MSOFA score ≥7) identified true positive 33 cases for death, false positive 1 case, false negative 6 cases and true negative 20 cases confirmed by patient's outcome. We concluded that there is a positive correlation (r=0.323; p=0.014) between CRP status with MSOFA score, positive correlation (r=0.402; p=0.002) between MSOFA score with MSOFA score and CRP combined and a positive correlation (r=0.999; p=0.001) between CRP level with MSOFA score and CRP combined.

Association of Hypertension with Serum Estrogen Level in Postmenopausal Women.

Hypertension is a chronic and debilitating disease. Its complications give rise to cardiovascular diseases, stroke in Postmenopausal women. Estrogen deficiency that develops during menopause is likely the etiological factor for development of hypertension in postmenopausal women. Increased incidence of cardiovascular diseases in postmenopausal women may be due to hypertension caused by lower level of estrogen hormone. The study was carried out to observe the association of hypertension with serum estrogen level in postmenopausal women. This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, during the period of January 2011 to December 2011. A total number of 90 female subjects were selected from different areas of Dhaka city. Among them, 60 postmenopausal women with age ranging from 50 to 60 years were taken as study group and 30 apparently healthy premenopausal women with age ranging from 20 to 30 years were included as control group for comparison. Systolic blood pressure and diastolic blood pressure were recorded in both groups. Serum estrogen level was estimated in order to assess the hormonal level of both groups. Data was analyzed by Unpaired Student's 't' test and Pearson's co-efficient (r) test as applicable. The value of systolic blood pressure was higher in postmenopausal women than those of premenopausal women and result was statistically significant. The level of diastolic blood pressure was also significantly (p<0.001) higher in postmenopausal women in comparison to those of premenopausal women. In postmenopausal women serum estrogen level was lower than premenopausal women and serum estrogen level showed negative correlation with systolic and diastolic blood pressure levels. All these correlation were statistically non significant. Present study revealed that there is association of hypertension with serum estrogen level in postmenopausal women.

EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target.

BACKGROUND: The aim of this study was to investigate the patterns of epidermal growth factor receptor (EGFR) overexpression, EGFR gene amplification, and the presence of activating mutations in the tyrosine kinase domain of this gene in squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas of the uterine cervix. METHODS: The EGFR expression, amplification, and mutation in cervical carcinomas were assessed by immunohistochemistry, fluorescence in situ hybridisation, and PCR-SSCP, respectively, and correlated with clinical data collected by a retrospective chart review. A functional assessment was performed by inactivating EGFR in cervical cancer cells with the potent inhibitor AG1478. RESULTS: Immunohistochemical analysis revealed that 6 out of 59 (10.2%) cervical squamous cell carcinomas showed significant amplification of the EGFR locus, whereas none of the 52 adeno/adenosquamous cell carcinomas had detectable EGFR amplification (P<0.05). The EGFR amplification significantly correlated with shorter overall survival (P=0.001) in cervical squamous cell carcinomas. Multivariate analysis showed that EGFR gene amplification was an independent prognostic factor for overall survival (P=0.011). None of the squamous cell carcinomas (0%: 0 out of 32) had detectable oncogenic mutations in EGFR exons 18 through 21. The frequencies of KRAS and BRAF mutations were very low in both squamous and adeno/adenosquamous cell carcinomas. Sensitivity of cervical cancer cells to AG1478 depended on the presence of EGFR overexpression. AG1478-induced EGFR inactivation in cell lines with EGFR overexpression significantly suppressed tumour development and progression in a mouse xenograft model. CONCLUSION: Our data suggest that EGFR signalling is important in a subset of cervical squamous cell carcinomas and that anti-EGFR therapy may benefit patients who carry the 7p11.2 amplicon in their tumours.

Recurrent synovial chondromatosis of the foot.

Synovial chondromatosis rarely occurs in the foot. We have diagnosed such a case in National Institute of Cancer Research and Hospital, Mohakhali, Dhaka. The patient came to us with a swelling in the dorsum of left foot. He had a history of operation but one year later swelling reappeared in the same place. Fine Needle Aspiration Cytology (FNAC) of the swelling revealed few atypical cells and diagnosed as a case of malignant neoplasm. Later on surgical intervention was done in the form of wide excision and final histopathology report came as Synovial chondromatosis. No special treatment was given other than periodical follow up. The patient has been responding well. There was no clinical or radiographic evidence of recurrence.

MSX2 is an oncogenic downstream target of activated WNT signaling in ovarian endometrioid adenocarcinoma.

Ovarian endometrioid adenocarcinomas (OEAs) frequently exhibit constitutive activation of canonical WNT signaling, usually as a result of oncogenic mutations that stabilize and dysregulate the ß-catenin protein. In previous work, we used microarray-based methods to compare gene expression in OEAs with and without dysregulated ß-catenin as a strategy for identifying novel ß-catenin/TCF target genes with important roles in ovarian cancer pathogenesis. Among the genes highlighted by the microarray studies was MSX2, which encodes a homeobox transcription factor. We found MSX2 expression was markedly increased in primary human and murine OEAs with dysregulated ß-catenin compared with OEAs with intact ß-catenin regulation. WNT pathway activation by WNT3a ligand or GSK3ß inhibitor treatment potently induced MSX2 and ectopic expression of a dominant negative form of TCF4 inhibited MSX2 expression in ovarian cancer cells. Chromatin immunoprecipitation studies demonstrated that ß-catenin/TCF directly regulates MSX2 expression via binding to TCF binding elements in multiple regions of the MSX2 gene. Notably, ectopic MSX2 expression was found to promote neoplastic transformation of the rodent RK3E model epithelial cell line and to enhance the invasiveness of immortalized human ovarian epithelial cells in vitro and ovarian carcinoma cells in vivo. Inhibition of endogenous MSX2 expression in ovarian endometrioid cancer cells carrying a ß-catenin mutation using shRNA approaches inhibited neoplastic properties of the cells in vitro and in vivo. Expression of MSX2 in selected ovarian carcinoma cells induced changes suggestive of epithelial-mesenchymal transition (EMT), but based on analysis of ovarian cell lines and primary tumor tissues, effects of MSX2 on EMT appear to be complex and context-dependent. Our findings indicate MSX2 is a direct downstream transcriptional target of ß-catenin/TCF and has a key contributing role in the cancer phenotype of OEAs carrying WNT/ß-catenin pathway defects.

A comparative study between microwave endometrial ablation and conventional surgical procedures for treatment of menorrhagia.

OBJECTIVE: To compare microwave endometrial ablation (MEA) using a new curved applicator with conventional surgical procedures in 26 patients with menorrhagia. STUDY DESIGN: Ten patients received MEA and 16 patients received conventional surgical procedures. Using a visual analog scale (VAS). MEA patients rated their menorrhagia, dysmenorrhea, and feelings of satisfaction from the procedure. The patients' intraoperative blood loss, operating time, and length of hospital stay were compared. RESULTS: Following MEA, the VAS scores were significantly decreased in the MEA patients for menorrhagia (p < 0.0001) and dysmenorrhea (p = 0.0002). The average VAS score regarding feelings of satisfaction for MEA was 8.9 (full score = 10). Mean blood loss, operating time, and mean length of hospital stay were significantly decreased in the MEA group compared to the conventional surgical procedure group (p < 0.0001). CONCLUSION: MEA successfully controlled menorrhagia and achieved a high rate of satisfaction among patients.

Exaggerated placental site mimicking placental site trophoblastic tumor: case report and literature review.

Exaggerated placental site is defined as a non-neoplastic trophoblastic lesion featuring exuberant infiltration into the endometrium and myometrium by intermediate trophoblasts and syncytiotrophoblasts. Exaggerated placental site can occur following normal or ectopic pregnancy, abortion, or hydatidiform mole. We encountered a case of reactive exaggerated placental site seven months following normal pregnancy that clinically mimicked placental site trophoblastic tumor. Few reports have described the clinical course, histopathology and differential diagnosis of exaggerated placental site; we present our patient's case together with histopathological observations and review of related literature.

Fractional allelic loss as a potential biomarker of risk prediction in early-stage mucinous ovarian tumors of low malignant potential.

Ovarian tumors of low malignant potential (LMP) appear to be intermediate between adenomas and ovarian carcinomas. Such tumors are often associated with a significantly better prognosis than for ovarian carcinomas. However, a subset of LMPs can progress and become lethal even in patients with early-stage disease. In order to seek sensitive diagnostic tools to monitor patients after surgical therapy, we performed a genome-wide scan for LOH in 37 early-stage mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reported to be associated with ovarian carcinoma. Fractional allelic loss (FAL) values were calculated as (loci scored with LOH)/(total informative loci) for each sample. With respect to tumor recurrence, high FAL values were more frequent in recurrent tumors than in non-recurrent tumors. Using the screening markers, FAL values for recurrent tumors were significantly higher than for non-recurrent tumors (19.8% vs 6.3%, respectively, p < 0.0001). Similar results were obtained using the hotspot markers (22.2% vs 7.1%, respectively, p < 0.0001). A significant correlation between FAL values obtained using screening markers and those based on hotspot markers was observed (R = 0.460, p = 0.003). Our findings suggest that a specific type of genetic instability (i.e., chromosomal instability, CIN) may exist in mucinous LMPs, and that this instability may indicate tumors with an aggressive biological nature. Therefore, FAL values may represent a new biomarker for risk prediction in early-stage mucinous LMP tumors.

A case of extremely chemoresistant pure pleomorphic rhabdomyosarcoma of the uterus associated with a high serum LDH level.

BACKGROUND: Pleomorphic rhabdomyosarcoma (RMS) of gynecologic origin is an exceedingly rare, highly malignant tumor. Only a few cases have been reported in the last decades. CASE REPORT: A 60-year-old postmenopausal woman presented with a high LDH level of unknown origin. Ultimately, she was diagnosed with pleomorphic RMS. She underwent total hysterectomy, bilateral salpingo-oophorectomy, left pelvic and paraaortic lymphadenectomy and partial omentectomy. Surgery was followed by systemic chemotherapy and pelvic irradiation. Unfortunately, the patient did not respond to treatment. Her disease course correlated with the fluctuation of plasma LDH levels. Ultimately she died within 20 months of the diagnosis. CONCLUSION: It is important to have better insight and to set a standard multimodal treatment for adult RMS. In addition, plasma LDH levels can be considered as a prognostic marker for RMS, particularly in advanced stage.

KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer.

This study examined the status of KRAS and BRAF mutations, in relation to extracellular signal-regulated protein kinase (ERK) activation in 58 ovarian carcinomas to clarify the clinicopathological and prognostic significance of KRAS/BRAF mutations. Somatic mutations of either KRAS or BRAF were identified in 12 (20.6%) out of 58 ovarian carcinomas. The frequency of KRAS/BRAF mutations in conventional serous high-grade carcinomas (4.0% : 1/25) was significantly lower than that in the other histological type (32.3% : 10/31). Phosphorylated ERK1/2 (p-ERK1/2) expression was identified in 18 (38.2%) out of 45 ovarian carcinomas. KRAS/BRAF mutation was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage I, II (P<0.001), and p-ERK1/2 (P<0.001). No significant correlations between KRAS/BRAF mutations or p-ERK1/2 expression and overall survival were found in patients with ovarian carcinoma treated with platinum and taxane chemotherapy (P=0.2460, P=0.9339, respectively). Next, to clarify the roles of ERK1/2 activation in ovarian cancers harbouring KRAS or BRAF mutations, we inactivated ERK1/2 in ovarian cancer cells using CI-1040. Cl-1040 is a compound that selectively inhibits MAP kinase kinase (MEK), an upstream regulator of ERK1/2, and thus prevents ERK1/2 activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated cancer cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. This was evident in both in vitro and in vivo studies. The findings in this study indicate that an activated ERK1/2 pathway is critical to tumour growth and survival of ovarian cancers with KRAS or BRAF mutations. Furthermore, they suggest that the CI-1040-induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian cancers. Therefore, ovarian cancer patients with KRAS or BRAF mutations may benefit from CI-1040 treatment.

Therapy-related myelodysplasia and acute myeloid leukemia following paclitaxel- and carboplatin-based chemotherapy in an ovarian cancer patient: a case report and literature review.

Alkylating agents have strong leukemogenic potential. There are a number of recent acute myeloid leukemia (t-AML) cases related to previous paclitaxel exposure. These leukemias tend to be of aggressive subtypes with long-latency periods. Unlike previously reported cases, the present case was of the secondary acute megakaryoblastic myeloid leukemia (AML M7) subtype. Additionally, it did not harbor a translocation in chromosome 19. A 73-year-old woman was diagnosed with t-AML M7 with antecedent myelodysplasia. Leukemia followed a second induction of paclitaxel- and carboplatin-based chemotherapy for recurrent ovarian cancer. Her second induction began 25 months after completion of her first course of chemotherapy. The increased incidence of postpaclitaxel leukemia suggests a probable role for paclitaxel as a leukemogenic agent. It highlights the importance of assessing for leukemia risk factors prior to beginning paclitaxel therapy.