Amstrupcobb2947

Subsequent PCAT-1 knockdown impaired CAF-mediated stromal activation, and reversed chemoresistance and tumor growth in vivo. Overall, these findings demonstrate the versatile roles of PCAT-1 in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.The geriatric nutritional risk index (GNRI) is associated with mortality in several malignancies. We retrospectively analyzed whether the GNRI can predict long-term outcomes in 191 patients with esophageal squamous cell carcinoma (ESCC) after curative esophagectomies by evaluating their cancer-specific survival (CSS). In multivariate analyses, serum albumin (hazard ratio [HR], 2.498; p = 0.0043), GNRI (HR, 1.941; p = 0.0181), pathological tumor-node-metastasis (pTNM) stage (HR, 3.884; p less then 0.0001), and tumor differentiation (HR, 2.307; p = 0.0066) were independent prognostic factors for CSS. In pTNM stage I, multivariate analysis identified C-reactive protein (HR, 7.172; p = 0.0483) and GNRI (HR, 5.579; p = 0.0291) as independent prognostic factors for CSS. In univariate analyses in pTNM stages II and III, only low GNRI (p = 0.0095) and low serum albumin levels (p = 0.0119), respectively, were significantly associated with worse CSS. In patients with low GNRI, CSS was significantly worse than in those with normal GNRI (p = 0.0011), especially in pTNM stages I (p = 0.0044) and II (p = 0.0036) groups, but not in stage III group (p = 0.5099). Preoperative GNRI may sort patients into low- or high-risk groups for shorter CSS, especially in those with pTNM stage I and II ESCC.

Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in gynecologic cancer models.

Murine orthotopic models of ovarian (OVCAR5 and SKOV3ip1) and uterine (Hec1a) cancer were used to study the biological effects of L-Grb2 on tumor growth.

experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanisms and potential predictors of tumor response to L-Grb2.

Treatment with L-Grb2 decreased tumor growth and metastasis in orthotopic models of ovarian cancer (OVCAR5, SKOV3ip1) by reducing angiogenesis and increasing apoptosis at a dose of 15 mg/kg with no effect on mouse body weight. Treatment with L-Grb2 and paclitaxel led to the greatest decrease in tumor weight (mean ± SEM, 0.17 g ± 0.10 g) compared with that in control mice (0.99 g ± 0.35 g). We also observed a reduction in tumor burden after treatment with L-Grb2 and the anti-VEGF antibody B-20 (86% decrease in tumor weight compared with that in controls). Ovarian cancer cells with ErbB2 amplification (OVCAR8 and SKOV3ip1) were the most sensitive to Grb2 downregulation. Reverse phase protein array analysis identified significant dysregulation of metabolites (LDHA, GAPDH, and TCA intermediates) in ovarian cancer cells after Grb2 downregulation.

L-Grb2 has therapeutic efficacy in preclinical models of ovarian and uterine cancer. These findings support further clinical development of L-Grb2.

L-Grb2 has therapeutic efficacy in preclinical models of ovarian and uterine cancer. These findings support further clinical development of L-Grb2.Acute myeloid leukemia (AML) is a heterogeneous malignancy with the most common genomic alterations in NPM1, DNMT3A, and FLT3. Midostaurin was the first FLT3 inhibitor FDA approved for AML and is standard of care for FLT3 mutant patients undergoing induction chemotherapy [1, 2]. As there is a spectrum of response, we hypothesized that biological factors beyond FLT3 could play a role in drug sensitivity and that select FLT3-ITD negative samples may also demonstrate sensitivity. Thus, we aimed to identify features that would predict response to midostaurin in FLT3 mutant and wild-type samples. We performed an ex vivo drug sensitivity screen on primary and relapsed AML samples with corresponding targeted sequencing and RNA sequencing. We observed a correlation between FLT3-ITD mutations and midostaurin sensitivity as expected and observed KRAS and TP53 mutations correlating with midostaurin resistance in FLT3-ITD negative samples. Further, we identified genes differentially expressed in sensitive vs. resistant samples independent of FLT3-ITD status. Within FLT3-ITD mutant samples, over-expression of RGL4, oncogene and regulator of the Ras-Raf-MEK-ERK cascade, distinguished resistant from sensitive samples. Overall, this study highlights the complexity underlying midostaurin response. And, our results suggest that therapies that target both FLT3 and MAPK/ERK signaling may help circumvent some cases of resistance.

polio eradication initiatives started in 1988, this is almost the past 32 years following the WHA resolution 41.8 of eradicating polio by the year 2000. As of 2019, only 3 countries remained to be polio endemic globally, Afghanistan, Pakistan and Nigeria. The east and southern sub-region countries had shown progressive achievement towards polio eradication and to start with the African regional certification. The availability of sensitive AFP surveillance performance is among important strategies in the achievement of polio eradication. We, therefore, decided to conduct this assessment of AFP performance from 2012 to 2019 in the ESA sub-region have evidence documentation and support the certification process of the WHO AFRO region.

we reviewed all reported acute flaccid paralysis (AFP) cases from 19 countries in the ESA sub region with the date of onset of paralysis from 1 January 2012 to 31 December 2019. The data were run to descriptive analysis based on the personal characteristics and AFP surveillanceP surveillance performances from 2020. A further subnational surveillance performance analysis is suggested.

we observed an overall increase in the sensitivity of the AFP surveillance performance for the ESA sub-region countries from 2012 to 2019 using the national performance indicators. #link# The COVID-19 pandemic paused an operational challenge for AFP surveillance performances from 2020. A further subnational surveillance performance analysis is suggested.

we conducted a pilot study for transferring skills for intrauterine device (IUD) insertion and implants to primary health care workers (PHCWs) as well as to provide injectable contraceptives to community health workers (CHWs) in 20 Health Centers in the Tougan Health District. This was aimed to increase access to contraceptive methods in Burkina Faso. Moreover, the purpose of this study was to assess the quality of family planning (PF) services offered by these delegated (PHCWs and CHWs).

we conducted a cross-sectional, descriptive, analytical study. Data collection was based on quantitative and qualitative methods. It included the 20 health centers in the study area and all providers (54) involved in contraceptive product supply (delegators and delegatees). Nineteen (19) recipients including 10 new contraceptive users were interviewed. link2 The method of data collection included the observation of FP services and of the working environment, document review and individual interviews. Data were analyzed using Eceptive methods to PHCWs as well as the provision of injectable contraceptives to CHWs, while maintaining a satisfactory level of FP service quality.

this purpose of this study was to improve the geographic coverage for long-acting contraceptive methods. Under certain conditions (skills-building, monitoring, coaching), it is possible to extend the transferring of skills for long-acting contraceptive methods to PHCWs as well as the provision of injectable contraceptives to CHWs, while maintaining a satisfactory level of FP service quality.

Nigeria still has high newborn deaths and birth asphyxia remains a major cause. Birth attendants´ readiness to perform newborn resuscitation depends largely on their competence in basic resuscitation and availability of newborn resuscitation equipment to enable the various steps outlined in resuscitation guidelines to be applied quickly and appropriately. This study aimed to assess primary health care workers´ experience of neonatal resuscitation and audit primary health centres for availability of neonatal resuscitation equipment.

this descriptive cross-sectional study surveyed 106 primary health care workers (22 doctors, 84 nurses) randomly selected from 28 Primary Health Centres to document their experiences in newborn resuscitation and appraise the centres for availability of newborn resuscitation equipment. Experience in newborn resuscitation was obtained using a semi-structured questionnaire and audit was with a Proforma following on-site facility visits. Data was analysed using SPSS v20 and displayed in tables and graphs.

all health care workers had resuscitated newborns but only 58(57.4%) had ever used a bag and mask, 53(50%) used stethoscopes and 19(17.9%) had resuscitation protocol in their facilities. Fifteen (53.6%) health centres had functional newborn-specific bag and masks, 11(39.3%) had suction machines and 5(25%) had empty oxygen cylinders.

primary health care workers´ experience of newborn resuscitation is very limited and some primary health centres were grossly unequipped. Neonatal resuscitation training interventions and supplies of neonatal resuscitation equipment are urgently needed.

primary health care workers´ experience of newborn resuscitation is very limited and some primary health centres were grossly unequipped. Neonatal resuscitation training interventions and supplies of neonatal resuscitation equipment are urgently needed.Metabolic syndrome (MS) is considered as a cardiovascular risk factor and has become a major public health issue. It exacerbates the risks, which are already high among diabetics. The purpose of this study is to determine the rates of metabolic syndrome and other cardiovascular risk factors (CRFs) in type 2 diabetics. We conducted a cross-sectional descriptive and analytical study in the Department of Endocrinology at the Befelatanana General Hospital, Antananarivo, over a period of 7 months. Varespladib cell line of MS was based on IDF harmonized criteria (2009). A total of 219 patients with type 2 diabetes were involved in the study, of whom 189 had metabolic syndrome (86.30%). MS was predominant in female patients (55.88%). On average, the mean age of patients was 58,58 years, BMI was 24.28 kg/m2 and abdominal circumference was 87,40 cm. Diabetes developed, in average, over 4.36 years (75.8% of patients had imbalance). Apart from hyperglycemia, arterial hypertension (AH) was the most common component of MS, followed by hypoHDLemia, abdominal obesity and hypertriglyceridemia between the two genders. Other most commonly reported cardiovascular risk factors associated with diabetes were dyslipidemia, followed by overweight or obesity, albuminuria and smoking. Overweight or obesity were cardiovascular risk factors significantly associated with MS. MS rate was very high in type 2 diabetics with several other CRFs. Adequate management of these risk factors is necessary to reduce the number of patients with MS as well as its consequences in order to improve survival.