Category: Nevin Manimala

Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2431-2439. doi: 10.31557/APJCP.2022.23.7.2431.

ABSTRACT

OBJECTIVE: To investigate the expression of CD44v6 and RCAS1 and the presence of HPV in cervical cancer tissues, to determine serum RCAS1 levels, and to evaluate these components in correlation with clinicopathologic features and survival.

METHODS: A total of 52 patients consisting of 28 squamous cell carcinoma (SCC) and 24 adenocarcinoma cases, were studied. RCAS1 and CD44v6 expression was evaluated using immunohistochemical staining. HPV 16 and 18 E6 genes were detected using PCR, and serum RCAS1 concentrations were measured using ELISA. Associations between these factors and clinicopathologic features and survival were analyzed.

RESULTS: CD44v6 expression was significantly higher in SCC compared with that in adenocarcinoma (P<0.001). It also showed a significant relation to histologic grade (P<0.001) and tumor size (P=0.03). RCAS1 expression was higher in adenocarcinoma than in SCC (P=0.001), and it showed a borderline relation with histological grade (P=0.057). Overall survival was not significantly different in both CD44v6 and RCAS1 expression; however, FIGO stage (P=0.025) and tumor size (P=0.042) resulted statistically different. The pre-surgical treatment serum RCAS1 levels were not associated with any clinicopathological variables. The presence of HPV 16 E6 was higher in SCC, while the presence of HPV 18 E6 was higher in adenocarcinoma (P<0.001). Detection of HPV 16 E6 was significantly associated with expression of CD44v6. The presence of HPV both HPV 16 E6 and HPV 18 E6 was found in cancer tissues with RCAS1 expression, but without any statistical significance.

CONCLUSION: CD44v6 and RCAS1 expression seems to be involved in tumor proliferation and differentiation, but it is not implicated in the progression and invasion of cervical cancer infected by HPV. Pre-treatment levels of serum RCAS1 in cervical cancer are not a diagnostic and predictive biomarker.

PMID:35901351 | DOI:10.31557/APJCP.2022.23.7.2431

Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2333-2340. doi: 10.31557/APJCP.2022.23.7.2333.

ABSTRACT

OBJECTIVE: We aim to investigate the effect of curcumin on preventing cancer anorexia-cachexia syndrome (CACS) via through mechanism of inhibition on NF-kB signal pathway. Outcome measurement for primary end point was improvement of body tissue composition, and the secondary end points were body weight and body mass index, hand grip muscle strengthening, and safety.

METHODS: This is randomized, double-blind, placebo-controlled phase ll a study, 33 patients with CACS in solid malignancy were enrolled and randomized in 1:1 to receive oral curcumin (at a dose of 800 mg twice daily) or placebo for 8 weeks.

RESULTS: All parameters of body compositions were not statistically significant different between two groups, which were consist body fat mass [-1.25(SEM 0.87) vs. +0.63(SEM 0.55); p=0.119], skeletal muscle mass [-0.35(SEM 0.60) vs.+0.33(SEM 0.42); p=0.408] and percent body fat [-0.47(SEM 0.95) vs. -0.29(SEM 0.82); p=0.893] including with basal metabolic rate [-13.47(SEM 21.94) vs. +15.30(13.76); p=0.336]. The average of weight loss was also not statistically significant different between two groups. [-1.4 kg(SEM 0.89) in curcumin vs-1.12 kg(SEM 0.73), p=0.810]. Notably, patient with curcumin had less reduction of hand-grip muscle strength on both hands [Rt. handed: -2.47 in curcumin vs. -5.36 in placebo; p=0.318] [Lt. handed: -1.98 vs. -5.43; p=0.317], and basal metabolic rate than placebo group. Most adverse events were grade 1 on both groups similarly.

CONCLUSION: Curcumin was not shown to be superior to placebo with regard to increasing the body composition in cancer patients with CACS. However, curcumin might show some clinical benefits, including slow progression of hand-grip muscle strength loss, and basal metabolic rate. Further investigations should be explored.

PMID:35901339 | DOI:10.31557/APJCP.2022.23.7.2333

Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2351-2359. doi: 10.31557/APJCP.2022.23.7.2351.

ABSTRACT

OBJECTIVE: This study aimed to determine the presence of Epstein-Barr Virus (EBV) and Human papillomavirus (HPV) in breast cancer with patients from Northeast of Brazil, considering the molecular subtypes and also taking in account the relation with TP53 immunoexpression.

METHODS: Seventy-five samples of invasive breast carcinoma with no special type were selected from pathology archives at Federal University of Ceará. EBV was detected by In situ hybridization (ISH) and immunohistochemistry (IHC) and HPV was detected by PCR. ISH was performed using EBER1 probe (Shibata et al., 1991; Bacchi et al., 1996) while IHC was performed on histological formalin-fixed paraffin-embedded tissue samples (Hsu et al., 1981). PCR methodology (Haws et al., 2004) was used to amplify the genetic material of human papillomavirus. The amplification products were electrophoretic analyzed on 1% agarose gel. The data analyses were carried out using the statistical software EPINFO® version 6.04d and SPSS version 17.0 (SPSS Inc., Chicago, IL). Statistically significant differences were evaluated by the chi-square test and Fisher’s exact test and correlations between groups were analyzed by Spearman’s and Pearson’s rank correlation coefficient.

RESULTS: 69.4% of the cases were EBNA1 positives by IHC. EBNA1 positive tumors had lower Ki-67 index (0-40%), while EBNA1 negative cases had relevant higher Ki-67 index (41-100%) (p = 0.06). EBV was present in all tumor grades, with a high frequency in grade I and III tumors comparing to EBNA1 negative cases. No HPV positive cases were observed.

CONCLUSION: Regarding the results from this study, we support the hypothesis that EBV can be involved on breast tumorigenesis.

PMID:35901341 | DOI:10.31557/APJCP.2022.23.7.2351

Biomed Chromatogr. 2022 Jul 28. doi: 10.1002/bmc.5464. Online ahead of print.

ABSTRACT

Neuroinflammatory injury is one of the typical brain injuries after the body is exposed to radiation. It is mainly characterized by the release of inflammatory factors by activated microglia and peripherally invading lymphocytes. To provide early warning for nerve injury and early diagnosis of neurodegenerative diseases, it is of great significance to explore the biomarker candidates of neuroinflammatory injury. This study focused on the screening of small molecular biomarker candidates in peripheral blood from rats with neuroinflammatory injury induced by whole-brain irradiation. Rats were exposed to 0, 10, 10×3 and 30 Gy of cobalt-60 γ rays. Serum was collected on the 30th day after exposure and analyzed using RPLC and HILIC coupled with high resolution mass spectrometry based upon untargeted metabolomics. Biomarker candidates were investigated by comparing the 0 Gy group and three irradiation groups using univariate statistical analysis, PCA and OPLS-DA. Eleven biomarker candidates were putatively identified and four major altered metabolic pathways were found. The screened small molecular biomarker candidates could be used as a useful supplement to traditional biomacromolecule markers, and may be valuable for radiation protection, target therapy of inflammatory injury, and discovery of new target drugs for the prevention and cure of related neurodegenerative diseases.

PMID:35899750 | DOI:10.1002/bmc.5464

Ned Tijdschr Geneeskd. 2022 Jun 22;166:D6758.

ABSTRACT

Although it is generally known that a (statistical) association between a factor, i.e., determinant or independent variable, and outcome, i.e., dependent variable, does not directly provide evidence of a causal relation, in practice the distinction between associative and causal relationships often becomes fuzzy when interpreting prognostic factor research. We provide suggestions for interpreting the findings of prognostic factor research. It is important to assess the purpose and design of the study, including the statistical analysis. The actual evidence that prognostic factor research can provide is easily overestimated. In particular when associations between factors and outcome are estimated in a multivariable analysis, causal or predictive qualities can easily but wrongfully be attributed to a prognostic factor. It is generally advisable to refrain from judgments on the causal of predictive qualities of a prognostic factor purely based on a prognostic factor study. Findings from prognostic factor research are usually a good starting point for follow-up research, while the direct applicability of such findings in daily medical practice is often limited.

PMID:35899712

Foot Ankle Int. 2022 Jul 28:10711007221112090. doi: 10.1177/10711007221112090. Online ahead of print.

ABSTRACT

BACKGROUND: Lisfranc injuries are among the most debilitating injuries to the foot. Characterization of first tarsometatarsal (TMT) joint involvement in Lisfranc injuries is limited. Multiple studies have indicated that this joint is damaged in a variety of Lisfranc injury patterns, but there is sparse information regarding how often and in what form.

METHODS: A retrospective review was performed of operative Lisfranc fractures from 2010 to 2020 with patients identified by Combined Procedural Terminology codes. Hardcastle and Myerson Lisfranc injury classifications and computed tomography and radiograph characterizations of the first TMT joint were evaluated by 3 foot and ankle fellowship-trained orthopaedic surgeons. Radiographic characteristics were collected. Light’s kappa coefficient evaluated interrater reliability for injury classification. Injury mechanism and Lisfranc classification effects on the first TMT joint were further assessed using inferential statistics.

RESULTS: Of 71 patients with a Lisfranc injury of which 37 (52%) were high energy, 61 (86%) showed radiographic evidence of first TMT joint injury. A fragment was present in the TMT articular surface in 33 (47%) with median size = 8.7 mm and medial capsular avulsion in n = 25 (35%). Forty-eight patients (68%) had medial/lateral TMT joint incongruence ≥2 mm (median overhang = 4 mm), 21 (30%) had dorsal/plantar incongruence (median overhang = 6 mm). Angulation of TMT articular surfaces ≥5 degrees on the transverse/anteroposterior plane occurred in n = 32 (45%) and in n = 12 (17%) on the sagittal/lateral plane, which significantly differed between classifications (P = .020).

CONCLUSION: The overwhelming majority of Lisfranc midfoot injuries seen at our tertiary referral center had imaging evidence of damage to the first TMT joint (86%), and the incidence may be higher. The most common patterns of first TMT joint involvement we found were joint incongruity, articular surface fractures, angulation of the articular surfaces, and medial capsular ligament avulsion fractures. A better understanding of injuries to the first TMT joint can help orthopaedic surgeons with diagnosis.

PMID:35899684 | DOI:10.1177/10711007221112090

Br J Haematol. 2022 Jul 28. doi: 10.1111/bjh.18381. Online ahead of print.

ABSTRACT

Acute myeloid leukaemia (AML) is conventionally thought of as a medical emergency. However, several studies on the association of time from diagnosis to treatment with survival did not have concordant results. Here we analyse 55 985 AML patients from the National Cancer Database, and we show that in patients less than 60 years old a five-day delay in chemotherapy initiation leads to worse long-term survival. The difference is small [hazard ratio (HR) 1.05, 95% condidence interval (CI) 1.01-1.09 in multivariate analysis] but statistically significant. This study raises the issue of power to detect small differences in retrospective studies.

PMID:35899627 | DOI:10.1111/bjh.18381

Stat Med. 2022 Jul 28. doi: 10.1002/sim.9531. Online ahead of print.

ABSTRACT

The Cox proportional hazards model is commonly used to estimate the association between time-to-event and covariates. Under the proportional hazards assumption, covariate effects are assumed to be constant in the follow-up period of study. When measurement error presents, common estimation methods that adjust for an error-contaminated covariate in the Cox proportional hazards model assume that the true function on the covariate is parametric and specified. We consider a semiparametric partly linear Cox model that allows the hazard to depend on an unspecified function of an error-contaminated covariate and an error-free covariate with time-varying effect, which simultaneously relaxes the assumption on the functional form of the error-contaminated covariate and allows for nonconstant effect of the error-free covariate. We take a Bayesian approach and approximate the unspecified function by a B-spline. Simulation studies are conducted to assess the finite sample performance of the proposed approach. The results demonstrate that our proposed method has favorable statistical performance. The proposed method is also illustrated by an application to data from the AIDS Clinical Trials Group Protocol 175.

PMID:35899596 | DOI:10.1002/sim.9531

Ann Otol Rhinol Laryngol. 2022 Jul 28:34894221111223. doi: 10.1177/00034894221111223. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC).

METHODS: Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence.

RESULTS: One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence.

CONCLUSIONS: TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

PMID:35899590 | DOI:10.1177/00034894221111223

Brain. 2022 Jul 28:awac222. doi: 10.1093/brain/awac222. Online ahead of print.

ABSTRACT

Malignant brain tumours are the cause of a disproportionate level of morbidity and mortality among cancer patients, an unfortunate statistic that has remained constant for decades. Despite considerable advances in the molecular characterization of these tumours, targeting the cancer cells has yet to produce significant advances in treatment. An alternative strategy is to target cells in the glioblastoma microenvironment, such as tumour-associated astrocytes. Astrocytes control multiple processes in health and disease, ranging from maintaining the brain’s metabolic homeostasis, to modulating neuroinflammation. However, their role in glioblastoma pathogenicity is not well understood. Here we report that depletion of reactive astrocytes regresses glioblastoma and prolongs mouse survival. Analysis of the tumour-associated astrocyte translatome revealed astrocytes initiate transcriptional programmes that shape the immune and metabolic compartments in the glioma microenvironment. Specifically, their expression of CCL2 and CSF1 governs the recruitment of tumour-associated macrophages and promotes a pro-tumourigenic macrophage phenotype. Concomitantly, we demonstrate that astrocyte-derived cholesterol is key to glioma cell survival, and that targeting astrocytic cholesterol efflux, via ABCA1, halts tumour progression. In summary, astrocytes control glioblastoma pathogenicity by reprogramming the immunological properties of the tumour microenvironment and supporting the non-oncogenic metabolic dependency of glioblastoma on cholesterol. These findings suggest that targeting astrocyte immunometabolic signalling may be useful in treating this uniformly lethal brain tumour.

PMID:35899587 | DOI:10.1093/brain/awac222