Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.

Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment.

Tumor-associated macrophages (TAM) have been classified into an immunostimulatory M1 subset against microbes and malignancies, and an immunoregulatory M2 subset that secretes immunosuppressive cytokines in order to repair tissues damaged by malignancies. The infiltration of M2 in the tumor microenvironment is known to facilitate immunosuppression and tumor-promoting properties. In the present study, we investigated the phagocytic potential of these macrophage subsets in oral squamous cell carcinoma (OSCC) in relation to the expression of CD47, the 'don't eat me' signal against macrophages. The macrophage subsets M1 (induced by GM-CSF and IFN-γ) and M2 (induced by M-CSF and IL-10) were derived from the CD14(+) cells of healthy donors. Phagocytosis of the CFSE-labeled CD47(+) cell line HSC-3 by M1/M2 was assessed using flow cytometry and suppressed by an anti-CD47 neutralizing antibody or CD47 siRNA. Furthermore, CD68(+) and CD163(+) macrophage subset counts infiltrating tumor tissue and the expression of CD47 on cancer cells were examined immunohistochemically in 74 cases of OSCC, and their relationships with clinicopathological parameters or prognoses were determined. The phagocytic potential of M1 was similar to that of M2 in vitro. Phagocytosis by M1 increased in a CD47-dependent manner by the neutralizing antibody and siRNA, but did not in M2. An immunohistochemical (IHC) analysis revealed that the expression of CD47 did not correlate with macrophage subsets in peritumoral tissue or with any clinicopathological parameters; however, the stronger expression of CD47 by cancer cells and larger number of total macrophages/M2 were independently related to shorter survivals. Our results suggest that the expression of CD47 by cancer cells is related to evasion from phagocytosis, particularly that by M1 in vitro. IHC results indicate that various mechanisms are involved in the engulfing potential of TAM subsets in vivo.

Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.

The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6th administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7th administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7th administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.

[Sequential Chemoradiotherapy for Advanced Head and Neck Cancer: A Clinical Study with 33 Cases].

A total of 33 patients with advanced head and neck cancer (AHNC) treated with sequential chemoradiotherapy (SCRT) were retrospectively evaluated at Gunma University Hospital between 2009 and 2011. The regimen of SCRT was docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy (ICT), accompanied by docetaxel and cisplatin-based concurrent chemoradiotherapy (CCRT), and oral administration of TS-1 after that. The response rate was 61%, the 3-year overall survival rate was 42%, the non-tumor-bearing survival rate was 27%, and the tumor-bearing survival rate was 15%. Fourteen of 33 patients were tumor-free, and their 3-year overall survival rate was surprisingly 86%. On the other hand, 3-year overall survival rate in the remaining 19 patients was significantly low. To select good response cases for ICT was important. In such cases, TPF should be applied repeatedly, which achieved a 61% response rate even in AHNC. A long-term TS-1 oral medication suppressed cancer regrowth and contributed to long-term survival.

Immunological significance of the accumulation of autophagy components in oral squamous cell carcinoma.

The immunological significance of autophagy in the tumor microenvironment remains unclear. To explore the relationship between autophagy and anti-tumor immune responses, we investigated the expression of autophagy-related proteins and infiltration of immune cells using immunohistochemistry (IHC). The expression of three representative autophagy components, LC3, Beclin-1 and p62/SQSTM1, as well as the number of dendritic cells (DC), T cells and NK cells were examined by IHC in 74 patients with oral squamous cell carcinoma (OSCC). The relationship between the expression of autophagy-associated molecules and various clinicopathological parameters was also evaluated. The expression of both LC3 and p62/SQSTM1 in the peripheral site significantly correlated with an increase in the infiltration of T cells. Furthermore, the expression of p62/SQSTM1 and Beclin-1 correlated with that of HLA class I and class II in tumor cells, respectively. In addition, several unfavorable clinicopathological parameters correlated with an increase in the expression of LC3 in the peripheral site. The correlation observed between LC3 or p62/SQSTM1 and the infiltration of T cells suggests that autophagy may actively mobilize immune cells toward the cancer bed. Meanwhile, the three autophagy-associated proteins examined were linked to malignant potential and an unfavorable prognosis.

Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) have been shown to play an important role in angiogenesis, invasion, and metastasis. In the present study, we determined whether CAFs within the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) contributed to promoting immunosuppression and evasion from immune surveillance. Six pairs of CAFs and normal fibroblasts (NFs) were established from the resected tumor tissues of patients with HNSCC. The effects of CAFs and NFs on the functions of T cells were comparatively analyzed. CAFs expressed the co-regulatory molecules, B7H1 and B7DC, whereas NFs did not. The expression levels of cytokine genes, including those for IL6, CXCL8, TNF, TGFB1, and VEGFA, were higher in CAFs. T cell proliferation was suppressed more by CAFs or their supernatants than by NFs. Moreover, PBMCs co-cultured with the supernatants of CAFs preferentially induced T cell apoptosis and regulatory T cells over those co-cultured with the supernatants of NFs. A microarray analysis revealed that the level of genes related to the leukocyte extravasation and paxillin signaling pathways was higher in CAFs than in NFs. These results demonstrated that CAFs collaborated with tumor cells in the TME to establish an immunosuppressive network that facilitated tumor evasion from immunological destruction.

[Prediction of Post-operative Lymph Node Metastasis with a Molecular Biological Test in Head and Neck Cancer].

We assessed herein the post-operative lymph node metastasis in head and neck cancer, using the One-step nucleotide amplification (OSNA) method targeting matrix metalloproteinase 7 (MMP-7). Compared with the pathological test, the molecular biological test revealed more lymph node metastasis, resulting in poor prognosis. Six cases, of which the number of lymph node metastasis was the same between pathological and molecular biological test, survived. On the other hand, three of four cases, in which number of lymph node metastasis in the molecular biological test were larger than the pathological test, died from metastasis. We concluded that the pathological test underestimated metastasis, and OSNA with MMP-7 was useful for the prediction of post-operative lymph node metastasis.

Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck.

Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells (CSCs). Moreover, evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs. Histone deacetylase inhibitors (HDACi) have multiple biologic effects consequent to alterations in the patterns of acetylation of histones and are a promising new group of anticancer agents. In this study, we investigated the effects of two HDACi, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), on two CD44+ cancer stem-like cell lines from squamous cell carcinoma of the head and neck (SCCHN) cultured in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. Histone deacetylase inhibitors inhibited the growth of SCCHN cell lines in a dose-dependent manner as measured by MTS assays. Moreover, HDACi induced cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD44 and ABCG2, on SCCHN cell lines was decreased by HDACi treatment. In addition, HDACi decreased mRNA expression levels of stemness-related genes and suppressed the epithelial-mesencymal transition phenotype of CSCs. As expected, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel, had a synergistic effect on SCCHN cell lines. Taken together, our data indicate that HDACi not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter the cancer stem cell phenotype in SCCHN, raising the possibility that HDACi may have therapeutic potential for cancer stem cells of SCCHN.

Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck.

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population and have the potential to suppress immune responses via diverse mechanisms. In recent studies, a new subset of MDSC was identified by the markers CD14(+) and HLA-DR(-) in the peripheral blood from cancer patients. In this study, we investigated the proportions and characteristics of CD14(+) HLA-DR(-) cells in patients with squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage of CD14(+) HLA-DR(-) cells was significantly elevated in patients relative to healthy donors and the sorted CD14(+) HLA-DR(-) cells were able to suppress effectively both the proliferation and IFN-γ production of anti-CD3/anti-CD28 stimulated T cells, suggesting that CD14(+) HLA-DR(-) cells in patients with SCCHN contribute to the immune suppressive status. Furthermore, CD14(+) HLA-DR(-) cells revealed a higher level of CD86 and PD-L1 expression and transforming growth factor (TGF)-ß production than CD14(+) HLA-DR(+) cells. Addition of anti-CD86 mAb, anti-PD-L1 mAb and anti-TGF-ß mAb partially restored T-cell proliferation and IFN-γ production, respectively, indicating that the suppressive effects of CD14(+) HLA-DR(-) cells appear to be mediated by various molecules, including coinhibitory molecules and cytokines. Our data suggest that CD14(+) HLA-DR(-) cells act as potent immunosuppressive cells and particularly contribute to tumor escape from the host immune system in patients with SCCHN.

Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

Two Different Tracts and Origin of Pyriform Sinus Fistula.

OBJECTIVE: Suppurative acute thyroiditis is caused by pyriform sinus fistula (PSF), and PSF frequently elicits deep neck abscess. However, complete fistulectomy is the ideal management of PSF, and studies on surgical findings of PSF are exceedingly rare. This study aimed to reveal the origins of PSF, each route, and clinical presentation. METHODS: This is a multicenter study. We have conducted 19 complete fistulectomies of PSF in Japan, analyzed routes of the fistulas, estimated the origins, and investigated their histological and clinical findings. RESULTS: No recurrence was observed in all cases. Five of 12 cases showed thymic and/or parathyroid tissues around the fistulas, passing inside the inferior horn of thyroid cartilage, were regarded as having 3rd pouch origin, and tended to have low frequency of severe deep neck abscess. The remaining 7 cases originated from the 4th pouch running outside of the horn and showed frequent severe infection. CONCLUSION: PSF have 2 different routes depending on their generation and may present different clinical manifestations.

Effects of resilient denture liner in mandibular complete denture on the satisfaction ratings of patients at the first appointment following denture delivery.

PURPOSE: The purpose of this study was to investigate whether edentulous patients with a permanent acrylic resilient liner denture (RLD) in mandibles exhibit significant improvements in their satisfaction ratings at the first appointment following the delivery of RLD dentures when compared to those with conventional heat-activated acrylic resin dentures (ARD) in mandibles. METHODS: Seventy-four subjects were randomly allocated into RLD and ARD groups by a random permuted block within the strata method after written informed consent. A parallel-randomized controlled clinical trial at two centers was conducted from April 2004 to July 2006. The outcomes were satisfaction ratings with a 100 mm visual analog scale (VAS) involving general satisfaction as well as satisfaction related to chewing, speaking, cleaning, stability, retention, comfort, and esthetics. The pain rating was also measured by the VAS. The outcomes were analyzed by Student t-test and Pearson's correlation coefficient. RESULTS: A significant difference between the RLD and ARD group in the maxillary denture was only obtained in the satisfaction rating of speaking. A significant difference between the RLD and ARD groups for the mandibular dentures was obtained in every satisfaction rating. The pain rating of the RLD group was significantly lower than that of the ARD group. The satisfaction ratings of mandibular denture functions significantly correlated with ratings of comfort and pain. CONCLUSION: Despite the limitation of a short-term observation, the mandibular satisfaction ratings were dramatically higher in RLD wearers than in ARD wearers.

Influence of ultraviolet irradiation treatment on porcelain bond strength of titanium surfaces.

To determine the effect of titanium (Ti) surface modification by ultraviolet irradiation (UVI) on the bond strength between Ti and porcelain. Grade 2 Ti plates were allotted to five groups: sandblasted (SA), 15 min UVI (UV), SA+5 min UVI (SA+UV5), SA+10 min UVI (SA+UV10), and SA+15 min UVI (SA+UV15). After surface treatment, porcelain was added. A precious metal (MC) was used for comparison with Ti. The effects of 24-h storage at room temperature versus thermal cycling only at 5 and 55°C in water were evaluated. Subsequently, the tensile strength of each sample was tested. Data were analyzed using one-way analysis of variance and the Tukey test. In both the room temperature and thermal cycling groups, the MC and SA+15 min UVI samples showed significantly greater bond strengths than the other samples (p<0.05). UVI processing efficiently increases the bond strength between porcelain and the Ti surface.

A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis.

In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

Antifungal effect of acrylic resin containing apatite-coated TiO2 photocatalyst.

The purpose of this study was to develop an acrylic resin with antifungal properties by leveraging the photocatalytic activity of apatite-coated titanium dioxide (Ap-TiO2). Candida albicans was used for antifungal activity assay of the specimen plates under ultraviolet A (UVA) with a black light source. Statistically significant decreases in cell viability in acrylic resins containing 5 wt% and 10 wt% Ap-TiO2 were observed after irradiation for two, four, and six hours (P<0.01), when compared to the control. As for the flexural strength and modulus values of acrylic resins mixed with Ap-TiO2 and TiO2 particles, they varied before and after irradiation. Among the tested specimens, a 5 wt% content of Ap-TiO2 in acrylic resin exceeded the requirements of ISO 1567. It was thus suggested that acrylic resin containing 5 wt% Ap-TiO2 could exert antifungal effects on C. albicans, while at the same time maintain adequate mechanical properties for clinical use.

A study of the effects of irradiation on the polymerization of dual-cured self-etching bonding system using electron spin resonance (ESR) spectroscopy.

The purpose of this study was to investigate the effect of irradiation on the polymerization behavior of a bonding agent of a dual-cured self-etching bonding system. By means of electron spin resonance spectroscopy, it was shown that the concentration of polymer radicals in samples cured chemically without irradiation was closely similar to that in samples dual-cured under irradiation. There was no significant difference in the time required to reach the maximum spin concentration between these two sample groups, thereby showing that the radical generation rates were similar. Findings of this study revealed that the dual-cured self-etching bonding system tested in this study was effective in polymerization in regions where irradiated light could hardly reach.

Circulating tumor cells in patients with head and neck squamous cell carcinoma: Feasibility of detection and quantitation.

BACKGROUND: The purpose of this study was to present our findings that because circulating tumor cells (CTCs) exist in extremely low numbers, their detection and quantification are challenging. METHODS: Peripheral blood samples were collected from 32 patients with head and neck squamous cell carcinoma (HNSCC), and were subjected to the CellSieve Microfiltration Assay using a low-pressure filtration system. The CTCs captured by the filter were stained with an antibody cocktail (anti-cytokeratin (CK) 8, 18, and 19, anti-epithelial cell adhesion molecule (EpCAM), and anti-CD45 antibodies). RESULTS: The CTCs were detected in 29 of 32 patients (90.6%). Although patients with advanced disease had a significantly higher number of CTCs, the clinical N classification was not associated with the CTC count. After treatment, the CTC count showed a significant decrease. CONCLUSION: The CTCs were successfully detected and quantified in patients with HNSCC by using a low-pressure filtration system equipped with precision microfilters. Further studies using a larger number of patient samples and/or molecular analysis of CTCs are warranted.

Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages.

Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells. The gene expression level of ARG1, IL10, and TGFB1 was increased in CAF-educated cells. CAF-educated cells suppressed T cell proliferation more strongly than control cells, and the neutralization of TGF-ß IL-10, or arginase I significantly restored T cell proliferation. We then investigated the relationship between the infiltration of CAFs and TAMs using tissue samples obtained from patients with OSCC. The infiltration of CAFs was associated with the numbers of CD68-positive and CD163-positive macrophages. It also correlated with lymphatic invasion, vascular invasion, lymph node involvement, and the TNM stage. The infiltration of CAFs was identified as an independent prognostic factor in OSCC. Our results indicate that CAFs play important roles in shaping the tumor immunosuppressive microenvironment in OSCC by inducing the protumoral phenotype of TAMs. Therapeutic strategies to reverse CAF-mediated immunosuppression need to be considered.

Shear bond strength of veneering composite resin to titanium nitride coating alloy deposited by radiofrequency sputtering.

OBJECTIVE: The success of dental restorations utilizing composite resin over cast alloy has been variable and affected by micro-leakage. The purpose of this study was to investigate the shear bond strength between a composite resin and cast dental alloy coated with a layer of titanium nitride (TiN). METHODS: Cast disk specimens made of Au-Pd-Ag alloy were randomly divided into four groups. The first group was left uncoated as a control while one group was coated with a metal conditioner, and the other two were coated with TiN at either 200 or 500 W with a radiofrequency magnetron sputtering system. Each group was then bonded to one of two types of light-activated composite resin material. Shear bond strengths were tested and compared for each specimen. The bond strength of each group was analyzed by 2-way ANOVA and by post hoc multiple comparison tests (Fisher's PLSD). RESULTS: As the interaction among groups was not significant (p=0.27) by 2-way ANOVA, TiN coated groups were found to have improved shear bond strength compared with non-coated groups without metal conditioner for both resin composite materials by multiple comparison tests. Furthermore, TiN coating is significantly stronger than non-coated groups with metal conditioner for one of the two resin composite materials examined (p<0.01). CONCLUSIONS: The results suggested that metal surface modification by coated TiN represents a technique that may significantly improve the bond between the Au-Pd-Ag alloy and veneering resin composite.

Decreasing expression of glucose-regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma.

BACKGROUND: The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various human cancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC. METHODS: A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki-67. Microvessel density was determined by immunohistochemical staining for CD34 and p53. RESULTS: Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression-free survival (PFS). CONCLUSION: GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various human neoplasms. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1544, 2016.