Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and ...cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in
(encoding pP53 protein),
(encoding cyclin dependent kinase inhibitor 2A),
(encoding FAT atypical cadherin 1), and
(encoding lysine methyltransferase 2D), with the exception of
(encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.
The effects of sun exposure on the skin and specifically those related to pigmentation disorders are well known. It has recently been shown that blue light leads to the induction of oxidative stress ...and long-lasting pigmentation. The protective effect of an aqueous extract of
(Fernblock
) is known. Our aim was to investigate the action mechanism of Fernblock
against pigmentation induced by blue light from digital devices. Human fibroblasts (HDF) and murine melanocytes (B16-F10) were exposed to artificial blue light (a 400-500 nm LED lamp). Cell viability, mitochondrial morphology, and the expression of the mitogen-activated protein kinase (MAPK) p38, known markers involved in the melanogenesis pathway, were evaluated. The activation of Opsin-3, a membrane protein sensitive to blue light that triggers the activation of the enzyme tyrosinase responsible for melanogenesis in melanocytes, was also analyzed. Our results demonstrated that pretreatment with Fernblock
prevents cell death, alteration of mitochondrial morphology, and phosphorylation of p38 in HDF exposed to blue light. In addition, Fernblock
significantly reduced the activation of Opsin-3 in melanocytes and the photo-oxidation of melanin, preventing its photodegradation. In sum, Fernblock
exerts beneficial effects against the detrimental impact of blue light from digital devices and could prevent early photoaging, while maintaining skin homeostasis.
Oxidative stress is a harmful effect induced on the skin by polycyclic aromatic hydrocarbons (PAH), including benzoapyrene (BaP) air pollutants. This effect is amplified by the additive damaging ...effect of the sun, especially through the UVA light component. Besides being one of the main compounds that make up air pollution, BaP can also be found in tar, tobacco smoke, and various foods. In addition to its direct carcinogenic potential, BaP can act as a photosensitizer absorbing sunlight in the UVA range and thus generating ROS and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Fernblock® (FB) is an aqueous extract from the leaves of Polypodium leucotomos that has been proven to exert photoprotective and antioxidant effects on skin cells. In this study, we evaluate the potential of FB to prevent the damage induced by a combination of BaP and UVA light on human keratinocyte and mouse melanocyte cell lines (HaCaT and B16-F10, respectively). In particular, we have analyzed the capacity of FB to counteract the alterations caused on cellular morphology, viability, oxidative stress and melanogenic signaling pathway activation. Our data indicate that FB prevented cell damage and reduced oxidative stress and melanogenic signaling pathway activation caused by a combination of BaP and UVA light irradiation. Altogether, our findings support the fact that FB is able to prevent skin damage caused by the exposure to a combination of UVA and the air pollutant BaP.
Pembrolizumab (P) is approved in the first-line (1L) setting in patients with squamous cell carcinoma of the head and neck (SCCHN) with a CPS ≥ 1 and has shown promising activity in the ...locally-advanced (LA) setting. However, there are no alternatives for patients who are platinum-5FU (PF)-unfit and in need of a rapid tumor response. Taxanes are active agents in SCCHN that could effectively substitute 5FU as shown in Keynote-B10, Frail-Immune and DEPEND trials 1-3. We evaluated the combination of pembrolizumab plus platinum and taxanes (PCT) +/- prophylactic (p) G-CSF in PF-unfit patients at our institution.
Retrospective study of patients diagnosed with SCCHN and treated with PCT at Hospital Clínico Universitario San Carlos, Madrid (Spain). A descriptive study, as well as objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety in the 1L and in the LA setting, were analyzed.
Within the period August 2019 - October 2023, 18 patients (1L: n=6; LA: n=12) were identified. Among 1L: Male/Female: 2/4; age: 65y (56-86). Subsite: oral cavity (OC): n=5, larynx (n=1). Median CPS: 40 (5-80). No. combo PCT cycles: 6 (2-9). No. maintenance P cycles: 4 (1-8). ORR: 67% (2 CR, 2 PR, 2 SD). After a median follow-up (F-U) of 9 months (m) (1 -25), median PFS and OS were 8 m (4.7 - 11.3) and NR (NR-NR), respectively. pG-CSF in 4/6 pts. G3/4 toxicity: G3 neutropenia: 4/6, G3 thrombopenia: 1/6. There were no toxic deaths. Among LA: Male/Female: 8/4; age: 72y (47-96). P + wkCBDCA-paclitaxel: n=10/12; P + 3wkCBDCA-paclitaxel: n=1/12, P + 3wkCDDP-docetaxel: n=1/12. Subsite: oropharynx: n=3, OC: n=5, CUP: n=1, Sinonasal: n=3. Median CPS: 30 (3-100). No. combo PCT cycles: 3 (2-4). No. maintenance P cycles: 0 (0-4). ORR after PCT (n=10): 90% (4 CR, 5 PR, 1 PD). Post-PCT Tx: Surgery: n=3; CRTx: n=5; Maint P: n=6. After a median follow-up (F-U) of 4 m (0-34), median PFS and OS were 6 m (NR - NR) and NR (NR-NR), respectively. pG-CSF in 6/12 pts. G3/4 toxicity: G3 neutropenia: 6/12, G3 thrombopenia: 4/12, G3 pneumonia: 1/12, G3 IR-colitis: 1/12, G4 IR-transaminitis: 1/12. There were no toxic deaths.
Updated results for the LA population (as of March 2024) will be presented at the meeting.
PCT and particularly weekly PCT +/- pG-CSF is a highly effective and safe chemoimmunotherapy option for PF-unfit patients in need of a rapid response and a positive CPS, both in the 1L and LA settings. Trials with weekly PCT should be conducted in comorbid and/or elderly patients with LA and R/M SCCHN not candidates for high-dose CT and in need of rapid response.
Oxidative stress is a harmful effect induced on the skin by polycyclic aromatic hydrocarbons (PAH), including benzoapyrene (BaP) air pollutants. This effect is amplified by the additive damaging ...effect of the sun, especially through the UVA light component. Besides being one of the main compounds that make up air pollution, BaP can also be found in tar, tobacco smoke, and various foods. In addition to its direct carcinogenic potential, BaP can act as a photosensitizer absorbing sunlight in the UVA range and thus generating ROS and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Fernblocksup.® (FB) is an aqueous extract from the leaves of Polypodium leucotomos that has been proven to exert photoprotective and antioxidant effects on skin cells. In this study, we evaluate the potential of FB to prevent the damage induced by a combination of BaP and UVA light on human keratinocyte and mouse melanocyte cell lines (HaCaT and B16-F10, respectively). In particular, we have analyzed the capacity of FB to counteract the alterations caused on cellular morphology, viability, oxidative stress and melanogenic signaling pathway activation. Our data indicate that FB prevented cell damage and reduced oxidative stress and melanogenic signaling pathway activation caused by a combination of BaP and UVA light irradiation. Altogether, our findings support the fact that FB is able to prevent skin damage caused by the exposure to a combination of UVA and the air pollutant BaP.
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