ANTICANCER ACTIVITIES OF THIOSEMICARBAZIDES/THIOSEMICARBAZONES: A REVIEW

There have been tremendous development in the chemotherapy of cancer and researches are still developing new and more effective drugs to combat this disease. Thiosemicarbazides and thiosemicarbazone possess a wide range of biological applications. This key biological role is often related with their capability to inhibit the enzyme ribonucleotide reductase, similar to what is observed with potent anticancer drugs such as triapine and methisazone. Recent studies have revealed that thiosemicarbazones can inhibit topoisomerase II enzyme. This review discusses current advances of an emerging ‘new wave' of thiosemicarbazide/thiosemicarbazone and their metal complexes as potent anticancer agents, mode of action and toxicity caused by them

To compare trans-vaginal ultrasound colour doppler (TUCD) with hysteroscopy and guided endometrial biopsy in diagnosing abnormal uterine bleeding

Background: To compare trans-vaginal ultrasound Colour Doppler (TUCD) with hysteroscopy and guided endometrial biopsy in diagnosing abnormal uterine bleeding.Methods: A total of 50 consecutive and haemodynamically stable patients aged more than 40 years with abnormal uterine bleeding (AUB) were included in the study. Patients with pregnancy and probable cervical malignancy were excluded. All the patients were subjected to TUCD followed by hysteroscopic directed endometrial biopsy during the follicular phase of the menstrual cycle between 7th and 11th day to diagnose the underlying pathology. In postmenopausal female both TUCD and hysteroscopy were performed on any day. Results of both the procedures were compared.Results: The sensitivity and specificity of TUCD as compared to hysteroscopy in diagnosing polyp was found out to be 27.78% and 100%; for fibroid 100% and 84.4%; for endometrial hyperplasia 86.36% and 96.43%; for endometrial carcinoma 71.43% and 100%; and for endometrial atrophy 100% and 100%, respectively. After application of kappa statistics, the degree of agreement between the two diagnostic procedures was found to be 0.599 which was considered to be good.Conclusions: Conditions like fibroid, endometrial atrophy and cases of A-V malformation are better diagnosed with TUCD, while others like endometrial polyps, endometrial carcinoma are better detected on hysteroscopy. TUCD can diagnose most of the pathologies but not all, so it can be used as an adjunct to hysteroscopy to diagnose endometrial pathology, but can surely not replace hysteroscopy

Evaluating condom catheter balloon tamponade in non-traumatic postpartum haemorrhage resistant to medical management

Background: Obstetric haemorrhage remains the most important cause of maternal mortality worldwide accounting for 25% of maternal deaths annually. The aim of the study was to evaluate efficacy of a condom catheter assembly for uterine tamponade in the management of non-traumatic postpartum haemorrhage (PPH).Methods: It was a prospective interventional study done in a tertiary care hospital in New Delhi, India. Thirty three women with intractable PPH unresponsive to medical management were managed by uterine balloon tamponade using a condom-catheter assembly prior to surgical intervention.Results: The catheter successfully controlled haemorrhage in 31 out of 33 patients. In both the failed cases, hysterectomy was required. Among the failed cases there was one maternal death due to sepsis and multi-organ dysfunction syndrome (MODS). In cases where the balloon was successful, it was removed around 24 hours later and no further bleeding or complication was observed.Conclusions: Placement of a condom catheter balloon can successfully treat non-traumatic PPH refractory to medical management. It is simple, inexpensive, easily, available and in those with successful placement no procedure related morbidity was observed. The potential for it to be used by inexperienced operators in areas with limited resources makes it a useful tool in management of PPH

Evaluation of feto-maternal outcome using AFI and SDVP for amniotic fluid assessment; Which is a better method?

ABSTRACTBackground: Abnormal amniotic fluid volume (AFV) may be the only or earliest sonographic sign of an obstetrical problem. There is no clear consensus on the best method to assess amniotic fluid adequacy. The AFI and the SDVP are the more commonly employed techniques for assessing adequacy of amniotic fluid. This study aimed to compare the maternal and foetal outcome when amniotic fluid was measured by these two methods.Methods: Hundred pregnant women at >28 weeks gestation scheduled for test of biophysical score due to various risk factors were enrolled and divided in two groups of 50 each. In each group, amniotic fluid volume was determined by either calculating the Amniotic Fluid Index (AFI) or measuring the Single Deepest Vertical Pocket (SDVP). Oligohydramnios was declared at cut off of <5 for the former and <2cm for the later method respectively. Maternal and foetal outcomes were compared between the two groups.Results: Diagnosis of oligohydramnios was 45/50 in group I and 23/50 in group II (p<0.0001). Induction of labour was done in 70.0% in group I and 18% in group II (p<0.0001). Non-reassuring foetal heart rate was seen in 36.0% in group I and 14.0% in group II (p=0.011). Rate of caesarean delivery was significantly higher in group I, 42.0% in comparison of 20.0% in group II (p=0.017). NICU admission were 32.0% in group I and 18.0% in group II (p=0.106).Conclusions: SDVP is a better choice for determining amniotic fluid to avoid unnecessary interventions without any significant improvement in peripartum outcome measures

Phase I study of bosutinib, a src/Abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors

Purpose: Bosutinib, a potent ATP-competitive, quinolinecarbonitrile Src/Abl kinase inhibitor, was tested in this first-in-human phase I trial in patients with advanced solid tumor malignancies. Patients and Methods: This trial was conducted in 2 parts. In part 1 (dose escalation), increasing oral bosutinib doses were administered using a 3 + 3 design. In part 2 (dose expansion), approximately 30 patients each with refractory colorectal, pancreas, or non–small cell lung cancer were treated at the recommended phase II dose (RP2D). Primary efficacy endpoints for part 2 were median progression-free survival (colorectal and non–small cell lung) and median overall survival (pancreas). Results: In part 1, dose-limiting toxicities of grade 3 diarrhea (two patients) and grade 3 rash occurred with bosutinib 600 mg/day and the maximum tolerated dose identified was 500 mg/day. However, the majority of patients treated with 500 mg/day had grade 2 or greater gastrointestinal toxicity, and 400 mg/day was identified as the RP2D. The most common bosutinib-related adverse events were nausea (60% patients), diarrhea (47%), vomiting (40%), fatigue (38%), and anorexia (36%). Bosutinib had a mean half-life of 19 to 20 hours at the RP2D. A partial response (breast) and unconfirmed complete response (pancreas) were observed; 8 of 112 evaluable patients had stable disease for 22 to 101 weeks. However, the primary efficacy endpoints for part 2 were not met. Conclusions: Bosutinib was generally well tolerated in patients with solid tumors, with the main toxicity being gastrointestinal. The RP2D was 400 mg/day orally. Further study of bosutinib is planned in combination regimens

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P < 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)Tesaro; Amgen; Genentech; Roche; AstraZeneca; Myriad Genetics; Merck; Gradalis; Cerulean; Vermillion; ImmunoGen; Pfizer; Bayer; Nu-Cana BioMed; INSYS Therapeutics; GlaxoSmithKline; Verastem; Mateon Therapeutics; Pharmaceutical Product Development; Clovis Oncology; Janssen/Johnson Johnson; Eli Lilly; Merck Sharp DohmeThis article was published on October 8, 2016; 6 Month Embargo.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Vertical stripe correction in Hyperion image using wavelet transformation and singular value decomposition (SVD)

Vertical striping are quite common in Hyperion images. The removal of these stripes turns out to be an important step of noise correction along with atmospheric and other artifact correction. Often these corrections are applied on radiometric values in spatial domain or fequency domain. We have proposed a novel approach to correct these vertical stripes using wavelet transformation and singular value decomposition. In the first step, we proposed stripe identification based on the Eigen ratio of first and second Eigen values of vertical components (decomposed using wavelet transformation). This ratio is supposed to be very high for striped images and minimal for stripe free images. This is because of the contribution to first Eigen value of high frequency stripes. These high frequency stripes contributes tremendously to the first Eigen because of their dominance in vertical component. We have also proposed a threshold function to identify the bands that needs to be corrected. After the stripes identification and correction algorithm is appllied on respective bands, it is observed that proposed method successfully removed striping noise with high accuracy. Upon comparing the results of proposed method with various other methods, it is found that proposed method have an edge and performing better than rest of the methods. To assess the results, SNR value was calculated for all methods and found highest for the proposed method except Local Threshold approach. Local Threshold have better SNR probably because of intact noise (even in visual inspection but also present in frequency plot of vertical wavelet component) in these methods