Journal of cancer research and therapeutics最新文献

Background: Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15 months. Genetic alterations have been studied in detail; however, additionally, there is now growing evidence on the role of epigenetic alterations in glioblastoma. Recently, histone modification patterns have been found to have a significant part in gene expression and prognosis. However, further research in this field is warranted to establish its role for the betterment of these patients with the deadly disease.

Aims: To determine the immunohistochemical expression of histone modifications like histone-3-lysine-18 acetylation (H3K18Ac) and histone-4-lysine 20 trimethylation (H4K20triMe) in glioblastoma patients.

Materials and methods: This is a retrospective study of 48 glioblastoma patients who underwent surgery. Immunohistochemistry (IHC) for tri-methyl-histone-H4 (Lys20) (H4K20triMe) and acetyl-histone-H3 (Lys18) (H3K18Ac) was performed in paraffin-embedded tissues manually, and the expression was noted. Data on the mitotic index and overall survival was collected and statistically analyzed.

Results: The mean age was 50 years with a M: F ratio of 1.6:1. Out of 48 cases, 60% (28 cases) demonstrated positivity for H3K18Ac and 98% (46 cases) for H4K20triMe. The pattern of expression was nuclear with increased expression adjacent to necrosis and at the invasive front. The overall median Q score for H3K18Ac was 1/12 and for H4K20triMe was 6/12. No significant statistical significance was observed between histone expression, Ki67%, and overall survival.

Conclusion: Histone modification patterns are being explored in detail in an array of tumors. They also have a potential role in glioblastoma for risk stratification and instituting appropriate treatment based on the prognosis. Epigenetic changes like histone modification patterns, in addition to genetics, can pave the way for a better molecular understanding of glioblastomas and provide hope in the future to improve the survival of these patients with deadly diseases.

Context: 

Adjuvant radiation therapy plays an important role in the management of high-risk cervical cancer after radical hysterectomy or inadvertent hysterectomy. The prime concern with the use of dual modality is steep decline in sexual well-being in cervical cancer survivors. Intravaginal brachytherapy (IVBT) delivered by vaginal cylinder or ovoids is essential for local control but at the cost of impairment of sexual function.

Aim: 

The purpose of this study was to assess the sexual well-being of cervical cancer survivors, who underwent surgery followed by adjuvant radiation and compare the subgroups of ovoids with sorbo brachytherapy.

Settings and Design: 

This was an observational, cross-sectional, and analytical study, whereby we evaluated sexual function of cervical cancer survivors by the Female Sexual Function Index (FSFI) instrument.

Subjects and Methods: 

Seventy-five women, identified as cervical cancer survivors who had received adjuvant radiation and IVBT, were administered FSFI questionnaire in face-to-face interviews.

Results: 

The mean age of 75 interviewed women was 48.64 years. Fifty survivors had received IVBT with a sorbo applicator and twenty-five with ovoids. FSFI full score ranged from 4.4 to 32.40. The mean full score for the whole group was 11.3. The mean FSFI full score was 24.91 (± standard deviation [SD] 5.71) in the ovoid group versus 4.49 (± SD 0.35) in the sorbo group. On Pearson’s correlation analysis, age and type of brachytherapy were significantly correlated with FSFI full score (P = 0.006) with correlation coefficient of − 0.312 and − 0.948, respectively.

Conclusions: 

Sexual dysfunction was found prevalent in 83% of cervical cancer survivors. The patients treated with IVBT with sorbo had worse sexual functioning than those treated with ovoids.

In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.

Background: 

Radiofrequency ablation has become a favorable treatment modality for small hepatocellular carcinoma (HCC) recently; however, insufficient radiofrequency ablation (RFA) was shown to lead to enhanced invasiveness and metastasis of HCC in our previous study, while the underlying molecular mechanism has not been understood.

Materials and Methods: 

In order to explore the influence of the hypoxic microenvironment on residual cancer and cancer stem cell (CSC)-like characteristics of HCC cells in this process, an in vitro hypoxic model and an insufficient RFA mouse model were established with HCC cancer cell lines. Immunochemistry staining and western blot were used to examine the expression of hypoxia-inducible factor (HIF)-1α and liver CSC markers. The 3D colon formation assay, tumor cell invasion assay, and gene transfection assays were applied to test the change in liver CSC stemness and HCC cell invasion.

Results: 

After insufficient RFA treatment, the upregulated HIF-1α expression was associated with an increase in the CSC-like population in residual cancer. In vitro, hypoxic tumor cells showed aggressive CSC-like properties and phenotypes. Wnt/β-catenin signaling activation was shown to be necessary for the acquisition of liver CSC-like characteristics under hypoxic conditions.

Conclusion: 

Overall, the aberrantly enhanced HIF-1α expression enhanced the liver CSC-like traits via abnormal Wnt/β-catenin signaling activation after insufficient RFA, and the overexpressed HIF-1α would be a vital factor and useful biomarker during the HCC recurrence and metastasis.

Melanoma is a fatal malignant tumor with a high rate of metastasis. Liver metastasis of melanoma is always associated with insensitivity to immunotherapy and a poor prognosis. However, the combination of cryoablation, which is believed to stimulate the antitumor immune response in the body, with immunotherapy can improve the therapeutic response to this condition. Herein, we present the case of a 79-year-old woman with BRAF (B-Raf proto-oncogene) wild-type melanoma who later developed liver metastasis. The patient received intravenous antiprogrammed cell death 1 antibody, which showed poor efficacy, and subsequent treatment with immunotherapy combined with cryoablation yielded a partial response. However, after the second cryoablation, the patient refused further treatment due to a fear of bleeding. Therefore, only immunotherapy was provided, which resulted in disease progression. This report demonstrates the need to consider immunotherapy plus cryoablation for the treatment of liver metastases in patients with BRAF wild-type melanoma.

Abstract: The incidence of 5-Fluorouracil (5FU)- induced leukoencephalopathy is <5% among the patients treated with this agent. It may present with disorientation, confusion, agitation, seizure, and coma. It should be suspected when patients present with any of these symptoms during or immediately after 5FU chemotherapy. Early detection of drug-induced leukoencephalopathy is important as the clinical symptoms can be reversed by early discontinuation of the drug. Therefore, clinicians should be aware of the possibility of this adverse neurologic effect of 5FU. We describe the case of a 35-year-old female with carcinoma esophagus with 5FU-induced leukoencephalopathy.

Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor that is common among adults. This aggression is due to increased invasion, migration, proliferation, angiogenesis, and decreased apoptosis. Plant-based compounds have a high potential to be used as an anticancer agent due to their various mechanisms and less undesirable side effects. Potentilla fulgens is a medicinal plant, and methanolic root extract of P. fulgens (PRE) has anti-inflammatory and anticancer properties.

Objective: In this study, we aimed to investigate antiproliferative effect of PRE on U118 and T98G glioblastoma cancer cells and to reveal which molecular signaling pathways regulate this mechanism of action.

Materials and methods: The effect of PRE on cell viability of GBM cells was investigated by MTT assay. Involvement of PRE with cell growth and survival signaling pathways, phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR and c-Src/signal transducer and activator of transcription 3 (STAT3), was examined using Western Blot.

Results: PRE reduced cell viability of GBM and human dermal fibroblast (HDF) cells in a dose-and time-independent manner. PI3K expression/phosphorylation level remained unchanged in both GBM and HDF cells after PRE treatment, but Akt/mTOR signaling pathway was downregulated in PRE-treated cells. PRE treatment did not affect c-Src expression/phosphorylation level in GBM cells; however, expression of c-Src was suppressed in HDF cells. Similar results were observed for STAT3 expression and phosphorylation status.

Conclusion: PRE has the ability to suppress cell viability in GBM cells, by targeting the Akt/mTOR signaling pathway.

Purpose: This study aimed to report 12 years of experience in the development of a quality assurance system in radiation oncology in a university hospital.

Material and methods: We developed the Quality Assurance Program in Radiation Oncology (QUAPRO) in 2008 to detect treatment deviation in the radiotherapy (RT) process with three steps of near-miss detection: simulation and prescription (primary check, PC), treatment planning (secondary check, SC), and treatment delivery process (tertiary check, TC). We transferred our paper-based medical records to electronic-based radiotherapy information systems (RTISs) in 2013. QUAPRO was completely integrated into RTIS in 2017. Since then, electronic-based incident reporting has been conducted. The program is called the Radiation Incident Learning System (RILS). The near-miss rates were compared during the three time periods: 2008-2012, 2013-2017, and 2017-2020.

Results: Five years of paper-based QUAPRO for 2008-2012 demonstrated a fluctuation in the checking ratio, with a gradually increasing rate of near misses of 3.5-19.7%. After electronic-based medical records were developed in 2013, the results revealed a dramatic increase from a rate of 2.7 to 4.2 in the number of checks per patient and achieved an increased rate of near misses of 24.7% for PC, SC, and TC. The rate of near misses gradually decreased to 5.3% after 2017 because of RT workflow improvement.

Conclusion: The analysis of 12 years in near-miss data reflected the effectiveness of our quality assurance program. The QUAPRO system can detect near-miss incidents in the whole RT workflow and illustrate the detection improvement when integrated into electronic-based medical records. Regular feedback and exploration of near-miss reporting are recommended for proper RT workflow improvement.

Aims: Cisplatin (cis-diamminedichloroplatinum(II), CP) is a platinum-based anticancer drug widely used in the treatment of solid malignancies. However, its side effects, particularly nephrotoxicity, are limiting factors in its clinic use. Rosmarinic acid (RA), a natural antioxidant compound, is reported to attenuate oxidative stress and associated pathophysiological outcomes. Our study aimed to explore the protective effect of RA against CP-induced acute kidney injury (AKI).

Materials and methods: We investigated the effect of RA at the dose of 100 mg/kg on AKI induced by CP (20 mg/kg) in mice. Various parameters of nephrotoxicity such as levels of serum electrolytes, albumin, and globulin were measured using standardized methods. Besides, a specific biomarker of damage to proximal tubular cells, kidney injury molecule-1 (Kim-1), was measured in the serum by ELISA. mRNA expression of Kim-1 and a transmembrane transporter, copper transporter 1 (Ctr1), was analyzed by quantitative reverse transcriptase-polymerase chain reaction. CTR1 expression was also analyzed by western blot technique.

Results: RA treatment restored the downregulated CTR1 , a renal transmembrane transporter in CP-treated mice. It was accompanied by a reduction in the level of serum albumin and globulin. Serum electrolytes such as Na+, K+, and Ca2+ in CP-treated mice were found to be restored with RA treatment. Moreover, RA also significantly downregulated the increased expression of nephrotoxicity biomarker KIM-1.

Conclusions: Overall, RA proved to be an effective nephroprotective compound which afforded protection at cellular and subcellular levels with an appreciable modulatory effect on a transmembrane transporter.

Abstract: Pseudoangiomatous stromal hyperplasia (PASH) is a benign entity of the breast and typically found incidentally or as a palpable mass. It usually affects women in the reproductive age group. In men, it is associated with gynecomastia. While the exact etiology is unknown, PASH is considered hormonally responsive. The mammography and ultrasonography findings are nonspecific. Grossly, PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slit-like spaces in dense collagenous stroma. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. PASH lesions should be surgically excised if increasing in size or associated with symptoms, also in cases of suspicious imaging findings or other lesions are synchronously diagnosed that require excision. In other small incidentally detected asymptomatic cases observation with clinicoradiological follow-up can be considered. It is associated with a good prognosis with no increased risk to develop breast cancer. Hence, the operating surgeon and pathologist should be aware of this not so uncommon entity so that patients are not subjected to unnecessary excision and subsequent physical and mental morbidity associated with it. In this article, we present a case report and also provide a brief review of the sparse literature on PASH, discussing clinical presentation, etiology and pathogenesis, radiopathological features, differential diagnosis, and the implications for further patient management and prognosis.