Functional Outcomes of Limb Salvage Surgery in Patients with Giant Cell Tumor of Bone of the Lower Extremities: A Retrospective Study

Giant cell tumor of the bone (GCTB) is a benign, locally aggressive neoplasm that is relatively rare, with a propensity to result in progressive bone destruction, and is associated with a high risk of recurrence. There is no widely held consensus regarding its ideal treatment. Worldwide, there are varying techniques ranging from intralesional curettage to resection of the lesion, supplemented with combinations of numerous adjuncts and fillers, depending on the resected amount and integrity of bone, as well as the preference of the surgeon. This was a cross-sectional study that included 20 patients who underwent limb salvage surgery for giant cell tumor of the bone of the lower extremities from January 2009 to February 2020 at two tertiary hospitals. The mean follow-up period was 37.3 months (SD=2.84). The extended curettage (EC) group had a mean Musculoskeletal Tumor Rating Scale (MSTS) score of 28.18 (SD=7.51) which is considered as an excellent outcome, while the resection (RS) group had an mean MSTS score of 19.67 (SD=11.02), which is considered as a good outcome. EC resulted to a total of eight complications (47%), while RS had one complication (33%). Prevalence of recurrence was noted to be 11.75% among those who underwent EC, while no recurrence was noted among those in the RS group. Use of bone cement as a filler was noted to have less recurrence as compared with the use of bone grafts, however were both were noted to result in excellent functional outcomes. Despite the prevalence of complications and recurrence of GCTB of the salvaged extremity in those who underwent EC, there is still report of excellent functionality. It is hence important to disclose all these possible outcomes and to stress the importance of compliance to follow-up for monitoring of these events.

In vitro Activity of Novel Cannabinoids Derived from Tetrahydrocannabinolic Acid on Various Human Tumor Cell Lines

The in vitro study of tetracannabinolic acid (THCA) derivatives ALAM027 and ALAM108 was carried out on the following human tumor cells: T47D (breast, ductal carcinoma), PC-3 (prostate, adenocarcinoma), HT29 (colorectal carcinoma), Caco-2 (colon, adenocarcinoma), A549 (lung, carcinoma), U87MG (human glioblastoma) and U266B1 (multiple myeloma). The in vitro effects of THCA derivatives ALAM027 and ALAM108 on cell growth inhibition and IC50 values were measured using the CellTiter Glo assay. The ALAM027 compound showed good growth inhibition in all cell lines tested with the exception of U87MG cells. The ALAM108 compound also suppressed the growth of U87 MG cells but had little effect on T47D tumor cells. In vitro studies of THCA derivatives ALAM027 and ALAM108 showed antitumor activity in all cell lines tested. The difference in the activity of these compounds in relation to the T47D and U87MG tumor cells may be indicative of different functional mechanisms.

Paracelsus Paradox and Drug Repurposing for Cancer

Dose is one of the parameters that any pharmacologist seriously considers when studying the effects of a drug. If the necessary dose to achieve a desired pharmacological effect is in a toxic or very toxic range for human use, the drug will probably fall out from further research. The concentration that a drug can reach at its target organ or cell is a direct consequence of the administered dose and its pharmacodynamic properties. Basic researchers investigate at the cellular level or eventually with xenografts. They use different concentrations of the drug in order to determine its cellular effects. However, in many cases, these concentrations require doses that are in the toxic range or well beyond any clinically achievable level. Therefore, in these cases, research is in the realm of Toxicology rather than therapeutics. This paper will show some examples about this exercise in futility which is time and resource consuming but that pullulates the pages of many prestigious journals. Many seasoned researchers seem to have forgotten the Paracelsus Paradox.

Role of Radiotherapy in the Management of Pancreatic Adenocarcinoma: Debate and Discordance in Clinical Trials

Pancreatic adenocarcinoma (PAC) is an extremely fatal malignancy with dismal outcome with standard treatment till date. Investigators are constantly in search of optimal treatment approach and radiation therapy (RT) remains in the centre of debate. Human pancreatic cancer cell lines have shown both intrinsic and hypoxia induced radio resistance, and RT has produced conflicting results as well in the various clinical trials. However, most of the American studies continued the use of RT as a potential treatment modality but the European school of thought is widely criticized for their ‘therapeutic nihilism’ towards radiation and faulty clinical trial designs. This article has reviewed the available literature on the evolving role of RT for the management of resectable and borderline resectable PAC and has highlighted the increasing trend towards the use of radiotherapy for both adjuvant and neo adjuvant treatment. With the advent of modern RT techniques, the acute and late toxicities are much less than the earlier time, and therefore augmented RT is expected to produce better clinical outcomes for the patients with pancreatic carcinoma.

The Loss of Heterozygosity of FHIT Gene in Sporadic Breast Cancer

The loss of heterozygosity (LOH) is a genetic event that can change gene function. FHIT is a potential tumor suppressor gene. Although the precise FHIT molecular mechanism of action is not well understood, evidences suggest that Fhit protein reduced levels are involved in mammary carcinogenesis. The aim of this study was to investigate if FHIT LOH could influence on sporadic breast cancer (BC) biological behavior, through its association with prognostic factors for sporadic BC.Tumor tissue and peripheral blood samples were analyzed using the microsatellite marker D3S1300. The findings were associated with clinicopathological parameters including overall survival. LOH was detected in 31.1%(52/167) of the informative BC’ cases. Considering clinical and pathological characteristics we have found no significant association with FHIT LOH status. The mean follow-up time was 80 months. After the Cox regression analysis two parameters remained associated with BC’s risk of death: TNM stage III and IV - HR = 3.74(95% CI, 1.16-12.1) P=0.027 and disease relapse HR = 3.14(CI 95% 1.26-7.80) P =0.014. This study shows that FHIT LOH by itself is not a prognostic factor for sporadic BC. Further researches are required to elucidate the functional role of FHIT LOH concerning to BC.

Spectrum of Pediatric Malignancies: An Observational Single Center Study from Western India

Cancer is a leading cause of death for children and adolescent worldwide. The cure rates in low middle-income countries are dismal (20%) in comparison to high income countries (80%). The first move is to assemble precise data on epidemiology of pediatric cancer across the country and its region wide variation. This study attempts to provide spectrum of pediatric malignancies from a tertiary care hospital in the state of Rajasthan, India. A total of 140 cases were studied retrospectively over a period of two years (April 2018-March 2020). Patients, 0-18 years of age that are diagnosed as a case of malignancy were included in this study. The records of these patients were retrieved and analyzed. Patients were stratified in 4 groups; 0-4 years, 5-9 years, 10-14 years and 15-18 years. Most of the patients fell in 15-18 year group (35.7%), followed by 5-9 year group (28.5%). Majority of cases, 67.8% were male. The male to female ratio is 2.1:1. Leukemia (40%) was the most common malignancy followed by lymphoma, retinoblastoma and malignant bone tumors. Acute lymphoblastic leukemia comprises majority (35/56) of leukemia. Retinoblastoma was predominant malignancy among <5-year children. In all other groups, leukemia was predominant. This study gauges the trend of pediatric malignancies at one of the largest tertiary care hospitals in Rajasthan, which is important in the planning and evaluation of health strategies. As we lack a dedicated pediatric cancer registry, such epidemiological studies play a significant part for this small but distinguished group of patients.

Fertility Cancer and Hereditary Risks in Soil Sample of Nasarawa, Nasarawa State, Nigeria

A survey of Fertility Cancer and Hereditary Risks in Soil Sample of Nasarawa was carried out. This study assessed the level of Fertility Cancer and Hereditary Risks in some part of Nasarawa using the gamma-ray spectrometry. The mean concentration for 40K was 645.29 ± 07.32 Bq/kg, for 226Ra was 28.43 ± 4.8422 Bq/Kg and for 232Th was 66.84 ± 2.0201 Bq/Kg. The average effective dose due to the ingestion was 0.36±0.1µSv/y which was approximately 1000 times lower than the world average effective dose. Radium equivalent activity Raeq (Bq/kg), alpha index and total cancer risk were found to be 161.44±8.08 Bq/kg, 0.142±0.02 and (0.21±0.05) ×10-5 respectively. UNSCEAR/ USEPA stipulated that; radium equivalent activity, alpha index, effective dose and total cancer risk should not exceed the limit of 370 Bq/kg, unity, 300 µSv/y and 1 ×10-4 respectively. Hence the values obtained in this work were within the acceptable limits. This implies that the ingestion or inhalation of soil is not associated with any radiological risk of concern.

Stromal and Tumor Glioma-Derived Cells with Similar Characteristics have Differences in α-Smooth Muscle Actin Expression and Localization

Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal component. The study of the interactions between the perivascular niche and its surrounding cells is of great value in unraveling mechanisms of drug resistance in malignant gliomas. In this study, we isolated the stromal diploid cell population from oligodendroglioma and a mixed population of tumor aneuploid and stromal diploid cells from astrocytoma specimens. The stromal cells expressed neural stem/progenitor and mesenchymal markers showing the same discordant phenotype that is typical for glioma cells. Moreover, some of the stromal cells expressed CD133. For the first time, we demonstrated that this type of stromal cells had the typical myofibroblastic phenotype as the α-SMA+ cells formed α-SMA fibers and exhibited the specific function to deposit extracellular matrix (ECM) proteins at least in vitro. Immunofluorescent analysis showed diffuse or focal α-SMA staining in the cytoplasm of the astrocytoma-derived, A172, T98G, and U251MG glioma cells. We could suggest that α-SMA may be one of the main molecules, bearing protective functions. Possible mechanisms and consequences of α-SMA disruptions in gliomas are discussed.

Postoperative radiotherapy and N2 non-small cell lung cancer prognosis: a retrospective study based on Surveillance, Epidemiology, and End Results database

Background: The purpose of this study is to clarify the significance of postoperative radiotherapy for N2 lung cancer.Aims: This study aimed to investigate the effect of postoperative radiotherapy on the survival and prognosis of patients with N2 lung cancer.Setting and design: Data from 12,000 patients with N2 lung cancer were extracted from the Surveillance, Epidemiology, and End Results database (2004-2012). Age at disease onset and 5-year survival rates were calculated.Statistical analysis: Survival curves were plotted using the Kaplan-Meier method. The univariate log-rank test was performed. Multivariate Cox regression were used to examine factors affecting survival.Results: Patients’ median age was 67 years (mean 66.46 ± 10.03). The 5-year survival rate was 12.55%. Univariate analysis revealed age, sex, pathology, and treatment regimen as factors affecting prognosis. In multivariate analysis, when compared to postoperative chemotherapy, postoperative chemoradiotherapy was better associated with survival benefits (hazard ratio [HR]= 0.85, 95% confidence interval [CI]: 0.813-0.898, P <0.001). Propensity score matching revealed that patients who had received postoperative chemoradiotherapy had a better prognosis than did patients who had received postoperative chemotherapy (HR=0.869, 95% CI: 0.817-0.925, P <0.001).Conclusion: Female patients and patients aged <65 years had a better prognosis than did their counterparts. Patients with adenocarcinoma had a better prognosis than did patients with squamous cell carcinoma. Moreover, prognosis worsened with increasing disease T stage. Patients who had received postoperative chemoradiotherapy had a better prognosis than did patients who had received postoperative chemotherapy. Postoperative radiotherapy was an independent prognostic factor in this patient group.

Research advance on the relationship between Wee1 and tumor genesis and progression

In the process of biological genetic information transmission, complete and correct genetic information can make cell mitosis proceed normally. In the development of most tumor cells, G2/M cell cycle checkpoint becomes the key checkpoint in the process of mitosis due to the lack of G1/S cell cycle checkpoint, which mainly depends on the abnormal DNA information blocked by Wee1 protein kinase in G2 phase to enter M phase and prolong the time of G2 phase to complete DNA sequencing So that the normal genetic information can be passed on. Wee1 protein kinase expression is significantly increased in most tumor cells, making it a potential target for tumor therapy.