Abstract Innate and adaptive immune cells patrol and survey throughout the human body and sometimes reside in the tumor microenvironment (TME) with a variety of cell types and nutrients that may differ from those in which they developed. The metabolic pathways and metabolites of immune cells are rooted in cell physiology, and not only provide nutrients and energy for cell growth and survival but also influencing cell differentiation and effector functions. Nowadays, there is a growing awareness that metabolic processes occurring in cancer cells can affect immune cell function and lead to tumor immune evasion and angiogenesis. In order to safely treat cancer patients and prevent immune checkpoint blockade-induced toxicities and autoimmunity, we suggest using anti-angiogenic drugs solely or combined with Immune checkpoint blockers (ICBs) to boost the safety and effectiveness of cancer therapy. As a consequence, there is significant and escalating attention to discovering techniques that target metabolism as a new method of cancer therapy. In this review, a summary of immune-metabolic processes and their potential role in the stimulation of intracellular signaling in TME cells that lead to tumor angiogenesis, and therapeutic applications is provided. 

/pdf/the-roles-of-metabolic-profiles-and-intracellular-signaling-eos5pzrc.pdf

The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors

Background: Leptin is a multifunctional adipose regulatorypeptide that has various actions in carcinogenesis. Mammarycarcinoma is one of the leading cancers in the world withtempted aspects to explore new prognostic factors.Aim of Study: We attempted to leptin expression in mam-mary carcinoma and its clinicopathological correlation.Material and Methods: Thirty-five cases of breast carci-nomas were studied for correlating leptin immunohistochemicalexpression with other available parameters.Results: The included cases' mean age is 57 years ±SD11.7. The majority of cases were invasive duct carcinoma. Asregards clinical pathological stages, stage IA (48.6%), stage IB (14.3%), stage IIA (14.3%), stage IIIA (2.9%), stage IIIB (14.3%), and finally stage IIIC (5.7%). Leptin immunostain was positive in 60% of studied mammary carcinoma cases and negative in 40%. Five cases of peri-tumoral fibrocystic disease were studied; all showed leptin positivity in ductal cells. Correlating leptin immunohistochemistry results with other findings, we found that significant relationship was found between leptin staining and mammary carcinoma histopathological type. Most invasive duct carcinoma (NST) showed positive leptin immunostaining (67.9%). On the other hand, most cases of the other types (lobular and mixed carcinomas) showed negative staining (71.4%) (p-value 0.027). Leptin immunostaing had insignificant correlation to T stage, grade, tumor lymphovascular emboli and perineural infiltration. As regarding tumor lymph nodal metastasis, most of cases without nodal metastasis (N0) were leptin-positive (76.5%) with significant p-value of 0.025. A significant relationship was detected between leptin immunostaining and clinicopathologic staging as well as molecular subtype. Estrogen-positive cases significantly correlate with leptin, with p-value of 0.0001. This also was observed with progesterone positivity, with p-value of 0.002. No significant relationship was found between leptin and Her-2 as well as Ki-67.Conclusion: Leptin immunostain can be of an extremehelp in mammary carcinoma prognosis.

https://mjcu.journals.ekb.eg/article_153810_c54251c0923b7a9dea5cdd79d4086cbe.pdf

Immunohistochemical Expression of Leptin in Mammary Carcinoma

Background The discrimination between chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO) has been a topic of concern in medicine. Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to study the possible differentiation concepts between ChRCC and RO.
Aim We attempted to study the pathological features of RO and ChRCC and correlate them focusing on the reliability of leptin immunostain use as a tool in differentiation.
Materials and methods A total of 25 cases of renal tumors (17 RO cases and eight ChRCC ones) were studied for clinicopathological features’ correlation and leptin immunohistochemical expression.
Results The included cases’ mean±SD age was 53.1±12.7 years, with range of 28–72 years. The male sex slightly exceeded the female one in prevalence of studied renal neoplasms (52 vs. 48%, respectively). Regarding the size of oncocytoma tumors in gross examination, it had a mean±SD of 5±2 cm, whereas that of ChRCC was 7±4 cm. The central scar is present in only four (23.5%) cases of oncocytoma, being absent in most cases (13 cases, 76.5%). In ChRCC, the nuclear grade 2 is the most common in the studied group (62.5%). Regarding leptin immunostaining scores, positive score was found in 13/17 oncocytoma cases, and only 2/8 cases of ChRCC showed nuclear leptin stain, with significant P value of 0.028. Oncocytoma leptin-positive cases represented 86.70%, whereas those of ChRCC represented 13.30% of total cases. Leptin sensitivity was estimated to be 76.5%, specificity 75.0%, positive predictive value 86.7%, negative predictive value 60.0%, with overall accuracy of 76%.
Conclusion Leptin immunostain can be of an extreme help in differentiating ChRCC and RO.

The reliability of leptin immunostain use for differentiating renal oncocytoma and chromophobe renal cell carcinoma

Carcinoma of the Colon and Rectum.

BackgroundThe occurrence of distant metastases in colorectal cancer (CRC) is the most important parameter in assessment of the prognosis of patients with CRC. Epithelial–mesenchymal transition (EMT) is the process that is incriminated in the occurrence of metastatic spread in CRC. Snail-1 is a zinc-

Snail-1, ALDH1, and claudin-1 tissue proteinexpression in patients with colorectal cancer:clinicopathological and prognostic implications

Characterization of an ovarian lesion is a diagnostic challenge. A correct preoperative assessment is of great importance so as to arrange adequate therapeutic procedures. The aim of the current study is to evaluate the diagnostic performance of functional MRI in differentiation between malignant, borderline, and benign ovarian masses. This study included 56 adnexal lesions. Bilateral synchronous ovarian lesions are detected in 16 cases. Postoperative histologically proved to be benign in 17 (30%), borderline (low potential malignancy) in 12 (22%), and malignant in 27 (48%). The overall diagnostic performance of conventional MRI in the diagnosis of adenexal lesion was a sensitivity of 74%, specificity of 47%, positive predictive value (PPV) of 76%, negative predictive value (NPV) of 44%, and an accuracy of 66%. Functional pelvic MRI examination showed an increase in overall diagnostic performance compared to conventional values with the highest sensitivity of 90% and NPV of 67% using DWI, and the highest specificity of 88%, PPV of 94%, and an accuracy of 82% using DCE MRI. Functional MRI in conjugation with conventional MRI plays a key role in the ovarian lesion detection, characterization, and staging. Functional MRI is currently being evaluated as possible predictive and prognostic biomarkers in ovarian lesions.

/pdf/functional-mri-in-the-pre-operative-assessment-of-gi-rads-3-1pc24m19ag.pdf

Functional MRI in the pre-operative assessment of GI-RADS 3, 4, and 5 ovarian masses

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Papers

Immunohistochemical Expression of Leptin in Mammary Carcinoma

The reliability of leptin immunostain use for differentiating renal oncocytoma and chromophobe renal cell carcinoma

Snail-1, ALDH1, and claudin-1 tissue proteinexpression in patients with colorectal cancer:clinicopathological and prognostic implications

Functional MRI in the pre-operative assessment of GI-RADS 3, 4, and 5 ovarian masses