Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma

Pediatric Blood &Cancer, EarlyView.


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Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder cancer

Abstract

Purpose

A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC).

Materials and methods

127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(−)) groups.

Results

A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(−) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019).

Conclusions

Cancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.

https://ift.tt/2MIcUPR

Autophagy-regulating microRNAs: potential targets for improving radiotherapy

Abstract

Background

Radiotherapy (RT) is one of the most important therapeutic strategies against cancer. However, resistance of cancer cells to radiation remains a major challenge for RT. Thus, novel strategies to overcome cancer cell radioresistance are urgent. Macroautophagy (hereafter referred to as autophagy) is a biological process by which damaged cell components can be removed and accordingly represent a cytoprotective mechanism. Because radiation-induced autophagy is associated with either cell death or radioresistance of cancer cells, a deeper understanding of the autophagy mechanism triggered by radiation will expedite a development of strategies improving the efficacy of RT. MicroRNAs (miRNAs) are involved in many biological processes. Mounting evidence indicates that many miRNAs are involved in regulation of the autophagic process induced by radiation insult, but the underlying mechanisms remain obscure. Therefore, a deep understanding of the mechanisms of miRNAs in regulating autophagy and radioresistance will provide a new perspective for RT against cancer.

Methods

We summarized the recent pertinent literature from various electronic databases, including PubMed. We reviewed the radiation-induced autophagy response and its association of the role, function and regulation of miRNAs, and discussed the feasibility of targeting autophagy-related miRNAs to improve the efficacy of RT.

Conclusion

The beneficial or harmful effect of autophagy may depend on the types of cancer and stress. The cytoprotective role of autophagy plays a dominant role in cancer RT. For most tumor cells, reducing radiation-induced autophagy can improve the efficacy of RT. MiRNAs have been confirmed to take part in the autophagy regulatory network of cancer RT, the autophagy-regulating miRNAs therefore could be developed as potential targets for improving RT.

https://ift.tt/2lRs8GM

Cognitive impairment and morphological changes after radiation therapy in brain tumors: A review

Life expectancy of patients treated for brain tumors has lengthened due to the therapeutic improvements. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown.Technical evolutions aim at enhancing the therapeutic ratio. Sparing of the healthy tissues has been improved using various approaches; however, few dose constraints have been established regarding brain structures associated with cognitive functions.The aims of this literature review are to report the main brain areas involved in cognitive adverse effects induced by radiotherapy as described in literature, to better understand brain radiosensitivity and to describe potential future improvements.

https://ift.tt/2lPRyof

Predicting the pathological response to neoadjuvant chemoradiation using untargeted metabolomics in locally advanced rectal cancer

The present study aimed to identify a panel of potential metabolite biomarkers to predict tumor response to neoadjuvant chemo-radiation therapy (NCRT) in locally advanced rectal cancer (LARC).

https://ift.tt/2tZGSr6

CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

Abstract

Background

Neoadjuvant chemotherapy (NAC) is the standard therapeutic strategy for triple-negative breast cancer (TNBC). TNBC patients with residual disease after NAC have a significantly worse survival than those with pathological complete response (pCR); however, there is no apparent prognostic factor for non-pCR patients. Cancer stemness or epithelial–mesenchymal transition (EMT) might influence the sensitivity to chemotherapy.

Patients and methods

Forty-eight patients with TNBC who were treated with NAC were available were included in this study. The expressions of stemness marker CD44v9, EMT marker vimentin and BRCA1, and basal phenotype were evaluated with immunohistochemistry. The relationships between the expression of these proteins and the pCR rate and the prognosis, especially in the patients with residual tumors, were investigated.

Results

Among the 48 patients, pCR was achieved in 14 cases. High nuclear grade and basal phenotype in the pre-NAC samples were significantly correlated with pCR (p = 0.0458 and 0.0343). There were no significant relationships between the pCR rate and the expression of CD44v9, vimentin, or BRCA1. Achieving pCR was significantly correlated with longer distant metastasis-free survival (DMFS) (p = 0.0206). High CD44v9 expression was significantly associated with shorter DMFS (p = 0.0291). Among the patients in whom pCR was not achieved, high grade in the residual tumor cells, poor pathological response and high CD44v9 expression in the pre-treatment CNB samples were significantly correlated with a poor DMFS (p = 0.0433, 0.0406 and p = 0.0333). In addition, high grade in the residual tumor cells was significantly associated with high CD44v9 expression in the pre-treatment CNB (p = 0.0389).

Conclusions

High CD44v9 expression in pre-NAC samples was associated with poor prognosis in TNBC patients treated with NAC, especially for those in whom pCR was not achieved.

https://ift.tt/2Nk3aMM

Synchronous MALT lymphoma of the colon and stomach and regression after eradication of Strongyloides stercoralis and Helicobacter pylori

Mucosa-associated lymphoid tissue (MALT) is vital for host immunological surveillance against pathogens. MALT lymphoma, also known as extranodal marginal zone B cell lymphoma, is a non-Hodgkin's lymphoma subtype that predominantly arises in the gastrointestinal tract. Chronic Helicobacter pylori (H. pylori) infection is a common cause of gastric MALT lymphoma, although other infections are reported in association with extragastric MALT lymphomas. To our knowledge, here we report the first case of synchronous MALT lymphomas of the colon and stomach in the presence of Strongyloides stercoralis and H. pylori infections that resolved after eradication of both organisms.

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