Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy—An Integrated View into other Neoplasms and Chemokine Networks

Cutaneous melanoma accounts for only about 7% of skin cancers but is causing almost 90% of deaths. Melanoma cells have a distinct repertoire of mutations from other cancers, a high plasticity and degree of mimicry toward vascular phenotype, stemness markers, versatility in evading and suppress host immune control. They exert a significant influence on immune, endothelial and various stromal cells which form tumor microenvironment. The metastatic stage, the leading cause of mortality in this neoplasm, is the outcome of a complex, still poorly understood, cross-talk between tumor and other cell phenotypes. There is accumulating evidence that Interleukin-8 (IL-8) is emblematic for advanced melanomas. This work aimed to present an updated status of IL-8 in melanoma tumor cellular complexity, through a comprehensive analysis including data from other chemokines and neoplasms. The multiple processes and mechanisms surveyed here demonstrate that IL-8 operates following orchestrated programs within signaling webs in melanoma, stromal and vascular cells. Importantly, the yet unknown molecularity regulating IL-8 impact on cells of the immune system could be exploited to overturn tumor fate. The molecular and cellular targets of IL-8 should be brought into the attention of even more intense scientific exploration and valorization in the therapeutical management of melanoma.

Case Report: Combination of Olaparib With Chemotherapy in a Patient With ATM-Deficient Colorectal Cancer

Poly-ADP ribose polymerase (PARP) inhibitors are constantly increasing in their indications for use as anti-cancer treatment in various neoplasms, the majority of which are linked with BRCA deficiency. Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting “BRCAness” or homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. With the current report we present the case of a heavily pretreated 55-year-old male patient diagnosed with stage IV ATM-deficient CRC, who was effectively treated with an off-label olaparib-irinotecan combination after exhaustion of all available treatment choices; furthermore, we discuss the existing data providing evidence for the use of PARP inhibitors in ATM-deficient CRC and encourage the implementation of next-generation sequencing (NGS) in patients with no other available treatment options.

Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.

Two rare cases of cystic angiomatosis and a literature review

Cystic angiomatosis is a rare disease characterized by disseminated multifocal hemangiomatous and/or lymphangiomatous cystic lesions of the skeleton with possible visceral organ involvement. Only a few dozens of such patients worldwide have been described in the literature. This article presents two case reports of the patients admitted to the D. Rogachev NRMCPHOI with suspected Langerhans cell histiocytosis. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. During the investigation, multiple cysts of the skull bones, spine, pelvic bones and limbs, as well as of the spleen were found in both patients. A biopsy of the bone cysts of the skull revealed no data in favor of histiocytosis or other neoplasms. Cystic angiomatosis was diagnosed in both cases. This is a rare disease that should be kept in mind in the differential diagnosis in patients with cystic lesions of the bones and visceral organs.

Immunological configuration of ovarian carcinoma: features and impact on disease outcome

Epithelial ovarian carcinoma (EOC) is a relatively rare malignancy but is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. At odds with other neoplasms, EOC is virtually insensitive to immune checkpoint inhibitors, correlating with a tumor microenvironment that exhibits poor infiltration by immune cells and active immunosuppression. Here, we comparatively summarize the humoral and cellular features of primary and metastatic EOC, comparatively analyze their impact on disease outcome, and propose measures to alter them in support of treatment sensitivity and superior patient survival.

Minimal Residual Disease in Multiple Myeloma: Something Old, Something New

The game-changing outcome effect, due to the generalized use of novel agents in MM, has cre-ated a paradigm shift. Achieving frequent deep responses has placed MM among those neoplasms where the rationale for assessing MRD is fulfilled. However, its implementation in MM has raised specific questions: how might we weight standard measures against deep MRD in the emerging CAR-T setting? Which high sensitivity method to choose? Are current response criteria still useful? In this work, we address lessons learned from the use of MRD in other neoplasms, the steps followed for the harmonization of current methods for comprehensively measuring MRD, and the challenges that new therapies and concepts pose in the MM clinical field.

CDK4, CDK6/cyclin-D1 Complex Inhibition and Radiotherapy for Cancer Control: A Role for Autophagy

The expanding clinical application of CDK4- and CDK6-inhibiting drugs in the managements of breast cancer has raised a great interest in testing these drugs in other neoplasms. The potential of combining these drugs with other therapeutic approaches seems to be an interesting work-ground to explore. Even though a potential integration of CDK4 and CDK6 inhibitors with radiotherapy (RT) has been hypothesized, this kind of approach has not been sufficiently pursued, neither in preclinical nor in clinical studies. Similarly, the most recent discoveries focusing on autophagy, as a possible target pathway able to enhance the antitumor efficacy of CDK4 and CDK6 inhibitors is promising but needs more investigations. The aim of this review is to discuss the recent literature on the field in order to infer a rational combination strategy including cyclin-D1/CDK4-CDK6 inhibitors, RT, and/or other anticancer agents targeting G1-S phase cell cycle transition.

Knowledge and practice related to the pap smear test among cytopathologists

Cervical cancer is the third most common type of cancer amongst women, compared to other neoplasms, with a higher potential for prevention, slow evolution, and has a simple and effective screening test in its detection, cure when diagnosed early. The routine examination in Brazil for the prevention of this type of cancer is the Pap smear test. This study aimed to reveal the knowledge and practice regarding the Pap smear test among cytopathologists. A descriptive and exploratory research, a qualitative approach, performed with 21 cytopathologists, by e-mailing a data collection instrument, from March to April 2018. Data were treated using the Hierarchical Descending Classification in IraMuTeQ software and analyzed by the Discourse of the Collective Subject. The construction of the results was carried out based on aspects of the knowledge of the cytopathologists about the Pap smear, related to the importance of the completion of the post-graduation for its accomplishment, and aspects of cytopathologists practice regarding the relevance of performing the early diagnosis of cervical cancer. We conclude on the need to reorganize the activities in the work process of the health professionals involved in the Pap smear.

Type of recurrence, cause of death and second neoplasms among 737 patients with ductal carcinoma in situ of the breast: 15-year follow-up.

e12592 Background: The aim of the study is to assess the results of the treatment of 737 consecutive patients with DCIS with particular attention to the character of recurrences, other neoplasms and causes of deaths. Methods: A retrospective analysis was carried out of 737 consecutive DCIS patients treated in one institution in the years 1996-2011. The percentage of failures, causes of death, cumulated recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast conserving treatment BCT, breast conserving surgery BCS), was calculated. Results: 66 recurrences (42% DCIS, 58% invasive) were reported: 61 recurrences in the breast, 5 outside the breast. The comparison of mammography images before the initial treatment and after local recurrence revealed the true recurrence in the breast in 48/61 (79%) of cases. The cumulated recurrence risk after 15-year observation, after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2 %, respectively (p < 0.001). 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p < 0.001). 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively, p = 0.329. In the course of the whole observation period 124 other neoplastic lesions in 121 patients (16%) were reported including 58 (8%) contralateral breast cancers. Deaths due to DCIS progression were reported in 4 (0.5%) of patients. An overwhelming majority (74/86) of deaths was linked to the age of the patients or other diseases, including other neoplasms. Conclusions: The highest recurrence risk reported in patients after BCS was unacceptable and, moreover, it kept growing over the fifteen years of observation. 79% of recurrences in the treated breast were true recurrences. Local recurrences were effectively treated without influence on OS. The percentage of deaths due to DCIS was low.