The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression.

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM-specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens-promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME's potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.

Morphological and biochemical action of dipyrone on rat placenta.

1. The morphological and biochemical action of dipyrone (N-[2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl]-methylamino methanesulfonate, sodium monohydrate) on the placenta of albino rats was studied by means of karyometry of trophoblastic giant cells and by determinations of DNA, RNA and total protein contents. 2. The animals were treated with a single daily dose of 50 mg/kg body weight during 5 different periods: from the 9th to the 12th, 11th to the 14th, 13th to the 16th, 15th to the 18th or 17th to the 20th day of pregnancy. 3. Karyometric results showed that the nuclear volumes of placental cells in rats treated with dipyrone during the first 3 periods were significantly greater than in control animals and that, closer to term, no differences were observed in this regard. Only the animals treated from the 9th to the 12th day of pregnancy had higher placental contents of DNA, RNA and protein than the corresponding controls. 4. Our results showed that dipyrone had a blocking effect on placental cell division which occurs mainly in the initial steps of placental development.

Melanin repigmentation after gingivectomy: a 5-year clinical and transmission electron microscopic study in humans.

The epithelium-melanin unit is formed by the melanocytes and keratinocytes. There is little information available about the behavior of melanocytes after surgical injury. Five white patients with comparable gingival pigmentation underwent gingivectomy to remove bandlike melanin pigmentations for cosmetic reasons. Biopsy specimens were taken from gingivectomy sites and healing areas 2, 3, 6, 7, 15, 50, and 180 days and 1.5, 3, and 5 years after the procedure. Transmission electron microscopic study revealed melanocytes in the process of migration and undergoing mitosis 6 and 7 days postoperatively. These cells exhibited, in the 15-day specimens, renewal of their dendritic processes and the four different stages of melanosome development. Keratinocytes were devoid of pigmented material until 50 days postoperatively. Clinically, the intensity of the pigmentation varied among the patients. Two reached baseline coloration 1.5 years postsurgery, while three returned to baseline coloration by 3 years postsurgery. Thus, gingival resective procedures, if performed solely for cosmetic reasons, offer no permanent results. (Int J Periodont Rest Dent 1993; 13:85-92.)

Lysosomal depletion in macrophages from spleen and foot lesions of Leishmania-infected hamster.

Analysis of lysosomes through acid phosphatase cytochemistry at the electron microscopy level has been performed in spleen and foot lesions from Leishmania-infected hamsters. The results showed that there is lysosomal depletion in macrophages from Leishmania donovani chagasi-infected hamster spleen and similar findings were obtained from foot lesions of Leishmania mexicana amazonensis-infected hamsters. The distribution of acid phosphatase and thiamine pyrophosphatase was also examined in the Golgi apparatus. It was possible to demonstrate that the activity of ACP is absent in infected macrophages from spleen and foot lesions of Leishmania-infected hamster while the distribution of TPP was very similar in control and infected macrophages from both systems. These results provide evidence that the lysosomal depletion can occur at the ACP synthesis and/or glycosylation level.

Effects of dipyrone on the placenta of albino rats: morphological and biochemical aspects

The effect of dipyrone (N-2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-methyllamino methanesulfonate sodium monohydrate) on the placenta of 2 BAW albino rats was studied through Karyometry of trophoblastic giant cells and DNA, RNA and total protein determinations. The animals received a single daily dose of 50 mg/Kg body weight during different periods of pregnancy: from the 9th to the 12th, 11th to the 14th, 13th to the 16th, 15th to the 18th and 17th to the 20 thday. Control animals received a single daily dose of 0.5ml distilled water at the same time. Karyometric results showed a statistically significant increase in nuclear volumes of placental cells of rats receiving dipyrone during the first three periods, when compared to control groups. In the two groups that received the drug nearer to term there was no significant difference. Regarding DNA, RNA and total protein determinations, there was a statistically significant difference, for all of them, in the rats that received the drug from the 9th to the 12 th day of pregnancy when compared to the control group. There was no significant difference in the groups that received the drug after that period. The results show that dipyrone had a blocking effect on cell division and that this effect happens mainly in the initial period of placental development

The Golgi apparatus and GERL during postnatal differentiation of rat parotid acinar cells: an electron microscopic cytochemical study.

Morphological and cytochemical changes in the Golgi apparatus and GERL of differentiating parotid acinar cells were examined in Sprague-Dawley rats from 5 days to young adult. At day 5, the Golgi apparatus consisted of 3-6 narrow saccules, with short segments of GERL lying adjacent to the trans Golgi saccule. As the glands matured, the Golgi apparatus increased in size and the saccules became broadened and fenestrated reaching a maximum from days 15-20. The saccules subsequently narrowed slightly and by day 25 resembled those seen in young adults. Numerous cisternae of GERL could be seen at the trans face during this period. While the glands were maturing, marked changes occurred in the distribution of thiamine pyrophosphatase (TPPase) activity in the Golgi saccules. In the immature cells, TPPase activity was restricted to 1 or 2 trans Golgi saccules. However, by day 10 TPPase could also be localized in immature secretory granules and in GERL-like cisternae. Unreactive segments of GERL were also present. This pattern of localization persisted until day 20, after which the TPPase activity in the GERL-like cisternae diminished gradually until by day 40 TPPase again was localized in 1-2 trans Golgi saccules and an occasional immature secretory granule. Acid phosphatase (AcPase) activity was localized primarily in lysosomes in the very young animals and increased in GERL with age up to day 15. From days 15 to 20 there was a decrease in the amount of activity seen in GERL, but from day 20 on, the AcPase activity increased until it reached that seen in young adult animals. These results indicate that the presence of TPPase activity in GERL-like cisternae and immature secretory granules may be dependent upon the developmental as well as the physiologic state of the acinar cells and lend further support to the suggestion that GERL is derived from the trans Golgi saccules.

Biochemical modulation of the submandibular salivary gland of castrated male mice treated with anabolic steroids.

The possibility that 19-nortestosterone decanoate, an anabolic steroid which has no androgenic effect in mice, may promote the recovery of certain biochemical parameters of the submandibular gland of castrated mice had been studied. It was demonstrated that protein, RNA and sialic acid concentrations, as well as, protease, acid phosphatase and succinate dehydrogenase activities were found to be similar to control values in the castrated mice treated with 19-nortestosterone decanoate (anabolic steroid) or testosterone propionale. The effects on seminal vesicle and levator ani muscle were also considered. The interaction between 19-nortestosterone decanoale and androgen-binding receptors in the submandibular gland is discussed.

Immunohistochemical localization of erythropoietin in the rat and mouse submandibular gland.

There is a great deal of evidence to indicate that organs other than the kidney are involved in erythropoietin production. In this paper, it is reported that erythropoietin has been localized with an immunocytochemical method in the granular ducts of the submandibular glands of the rat and mouse.

[Biochemical study of nucleic acids of placenta and fetal liver and caryometric of trophoblastic giant cells and fetal hepatocytes of Rattus norvegicus albinus, during action of sodium 1-phenyl-2, 3-dimethyl-5-pyrazolon-methane sulfonate (Dipyrone) (author's transl)]. / Estudo bioquímico dos ácidos nucléicos da placenta e do fígado fetal e cariométrico das células gigantes trofoblásticas e dos hepatócitos fetais de Rattus norvegicus albinus, sob o efeito da 1-fenil-2,3-dimetil-5-pirazolona-4-metilamino-metanossulfato de sódio (Dipirona).

Female pregnant rats of 2BAW strain were divided in 2 groups: the 1st, received 50 mg/kg corporal weight of sodium 1-phenyl-2,3-dimethyl-5-pyrazolon-4-methylamino-methane sulfonate (Dipyrone), single dose daily, by i.p. injections, from 16th to 20th day of pregnancy; the 2nd, received 0,5 ml of distilled water, single dose daily, by i.p. injections, during the same period. All the animals were sacrificed 2 hours after the last injection. The biochemical results of nucleic acids in the placentas and fetal livers, and the caryometric data of trophoblastic giant cells and fetal hepatocytes, demonstrated that: 1. When compared the 2 groups, as much the nucleic acids levels (RNA and DNA) of placentas as the nuclear size of trophoblastic giant cells, do not presented statistical differences; 2. The biochemical levels of nucleic acids (RNA and DNA) of fetal livers decreased, while the nuclear size of hepatocytes increased in the experimental group, with reference to control group.