Advanced larynx cancer

Strome, Scott E.; Weinman, Eric C.

doi:10.1007/s11864-002-0037-9

Cited by 10 publications

(10 citation statements)

References 33 publications

(29 reference statements)

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“…F, persistence of Bcl-2 down-regulation. HN-4 cells received no treatment (5) or the combination of chemotherapy and radiation (n). At the indicated time points, mRNA was harvested and real-time PCR was done for Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis

Gelbard

Garnett

Abrams

et al. 2006

Clinical Cancer Research

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Purpose: The combination of systemic multiagent chemotherapy (5-fluorouracil + cisplatin) and tumor irradiation is standard of care for head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been shown that sublethal doses of radiation or chemotherapeutic drugs in diverse cancer types may alter the phenotype or biology of neoplastic cells, making them more susceptible to CTL-mediated cytotoxicity. However, little is known about the potential synergistic effect of drug plus radiation on CTL killing. Here, we examined whether the combination of two chemotherapeutics and ionizing radiation enhanced CTL-mediated destruction of HNSCC more so than either modality separately, as well as the basis for the enhanced tumor cell lysis. Experimental Design: Several HNSCC cell lines with distinct biological features were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Seventy-two hours postirradiation, tumor cells were exposed to an antigen-specific CD8 + CTL directed against carcinoembryonic antigen or MUC-1. Results: In three of three tumor cell lines tested, enhanced CTL activity was observed when the two modalities (chemotherapy and radiation) were combined as compared with target cells exposed to either modality separately. CTL-mediated lysis was MHC restricted and antigen specific and occurred almost entirely via the perforin pathway. Moreover, the combination treatment regimen led to a 50% reduction in Bcl-2 expression whereas single modality treatment had little bearing on the expression of this antiapoptotic gene. Conclusions: Overall, these results reveal that (a) CTL killing can be enhanced by combining multiagent chemotherapy and radiation and (b) combination treatment enhanced or sensitized HNSCC to the perforin pathway, perhaps by down-regulating Bcl-2 expression. These studies thus form the rational basis for clinical trials of immunotherapy concomitant with the current standard of care of HNSCC.

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Section: Discussionmentioning

confidence: 99%

Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis

Gelbard

Garnett

Abrams

et al. 2006

Clinical Cancer Research

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“…The BDI is a 21-item survey that captures information about symptoms of depression using ordinal scale responses ranging from 0 to 3. Studies have provided normative results categorized as normal (0-9), mild (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), moderate (21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and severe (Ն31) depressive symptoms. 31 The HNCI is a 30-item survey that measures HNC-specific outcomes in the areas of speech, eating, aesthetics, and social disruption.…”

Section: Methodsmentioning

confidence: 99%

“…Substantial progress in the reconstruction of the tongue, mandible, pharynx, and larynx has also been made. [19][20][21][22] Most of the major advances in the surgical treatment of HNC during the past 20 years have been directed primarily at improving functional status and QOL without compromising oncologic effectiveness.…”

mentioning

confidence: 99%

Long-term Quality of Life for Surgical and Nonsurgical Treatment of Head and Neck Cancer

El‐Deiry¹,

Funk²,

Nalwa³

et al. 2005

Arch Otolaryngol Head Neck Surg

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To compare the long-term, health-related quality-of-life outcomes in patients with advanced head and neck cancer (HNC) treated with surgery and postoperative radiation therapy (SRT) or concurrent chemotherapy and radiation therapy (CRT).Design: Matched-pair study comparing patients with advanced HNC treated with SRT or CRT at least 12 months after treatment. Patients completed 2 validated surveys addressing HNC-specific outcomes and depressive symptoms and provided information on employment and tobacco and alcohol use. Results for the 2 groups were compared using paired-sample t test and 2 analysis.Setting: University-based study. Patients: Patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, and larynx who underwent SRT or received CRT. Main Outcome Measures: Head and neck cancer-specific health-related quality of life from the Head and Neck Cancer Inventory and level of depressive symptoms from the Beck Depression Inventory.Results: The matching process resulted in 27 patients in each treatment group. The HNC-specific domain scores (with higher scores representing better outcomes) for CRT vs SRT were eating, 37.8 vs 40.8 (P=.69); speech, 65.1 vs 56.0 (P=.23); aesthetics, 80.3 vs 69.2 (P=.14); and social disruption, 69.7 vs 70.6 (P = .90). Overall healthrelated quality of life was 64.0 with SRT and 55.0 with CRT (P=.142). For the Beck Depression Inventory (with higher scores representing worse outcomes), patients who underwent SRT had a mean score of 9.6 compared with 11.6 for patients who received CRT (P =.42). Conclusion:As nonsurgical means of treating HNC have become more aggressive and surgical techniques have become more focused on function preservation and rehabilitation, the overall health-related quality of life resulting from these different approaches is similar.

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“…Despite continually evolving therapeutic options, we have witnessed little improvement in survival for patients with squamous cell carcinoma of the head and neck (SCCHN) over the past three decades (1). While immunotherapy has the potential to improve outcomes, broad clinical application will require improved understanding of the immuno-regulatory and cytotoxic potential of specific effector cell populations.…”

Section: Introductionmentioning

confidence: 99%

Isopentenyl Pyrophosphate–Activated CD56+ γδ T Lymphocytes Display Potent Antitumor Activity toward Human Squamous Cell Carcinoma

Alexander¹,

Maniar²,

Cummings

et al. 2008

Clinical Cancer Research

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138

151

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Purpose: The expression of CD56, a natural killer cell^associated molecule, on ah T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed on a subset of gy T cells. However, antitumor effector functions of CD56 + gy T cells are poorly characterized. Experimental Design: To investigate the potential effector role of CD56 + gy T cells in tumor killing, we used isopentenyl pyrophosphate and interleukin-2^expanded gyTcells from peripheral blood mononuclear cells of healthy donors. Results: Thirty to 70% of expanded gy T cells express CD56 on their surface. Interestingly, although both CD56+ and CD56 -gy Tcells express comparable levels of receptors involved in the regulation of gy T-cell cytotoxicity (e.g., NKG2D and CD94), only CD56 + gy T lymphocytes are capable of killing squamous cell carcinoma and other solid tumor cell lines. This effect is likely mediated by the enhanced release of cytolytic granules because CD56 + gy T lymphocytes expressed higher levels of CD107a compared with CD56 -controls following exposure to tumor cell lines. Lysis of tumor cell lines is blocked by concanamycin A and a combination of anti-gy T-cell receptor + anti-NKG2D monoclonal antibody, suggesting that the lytic activity of CD56 + gy T cells involves the perforin-granzyme pathway and is mainly gy T-cell receptor/NKG2D dependent. Importantly, CD56-expressing gy T lymphocytes are resistant to Fas ligand and chemically induced apoptosis. Conclusions: Our data indicate that CD56 + gy Tcells are potent antitumor effectors capable of killing squamous cell carcinoma and may play an important therapeutic role in patients with head and neck cancer and other malignancies.

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Advanced larynx cancer

Cited by 10 publications

References 33 publications

Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis

Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis

Long-term Quality of Life for Surgical and Nonsurgical Treatment of Head and Neck Cancer

Isopentenyl Pyrophosphate–Activated CD56+ γδ T Lymphocytes Display Potent Antitumor Activity toward Human Squamous Cell Carcinoma

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