Malignant Mesothelioma highly malignant disease in 2020

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for the radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with the survival of up to 1 year. However, the median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.


Summary – Most common primary pleura tumor

Malignant pleural mesothelioma is the most common primary pleura tumor and its aggressiveness is high. The most common cause is contact with asbestos and the incidence is still rising, although work with asbestos is already banned in developed countries. The diagnosis is based primarily on the medical history, clinical symptoms and immunohistochemical examination of the tumor sample. In the past 10 years, cisplatin-pemetrexed chemotherapy has been the primary treatment. A number of studies are underway with other biologically-targeted treatments, immunotherapy, and other drugs that can improve the prognosis of patients. The surgical approach is limited by the appropriate selection of patients and sufficient experience in the workplace. Extrapleural pneumonectomy or widespread pleurectomy is performed. However, even combination therapy with adjuvant or neoadjuvant chemotherapy or radiotherapy did not significantly prolong survival. There are several more Information about this on the web you can also check for more here

Paratesticular malignant mesothelioma. Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with a limited number of published cases. The emergence of this tumor is most often associated with asbestos exposure with a typical long latency between exposure and diagnosis. We present a case report of an eighty-year-old patient with a hydrocele. Before the operation, a relief puncture was performed several times for the extreme size of the hydrocele. Peroperatively, we found a voluminous septal hydrocele with significantly thickened containers, filled with hemorrhagic fluid, testis of physiological appearance and small atrophic epididymis. Due to the surgical finding, we indicated an orchiectomy at the patient’s age. The histologically surprising finding of malignant mesothelioma of envelopes. In another follow-up, scratch resistance appeared within six months. After its extirpation, histologically verified mesothelioma recurrence. The patient is now actively monitored.

Mesothelioma Molecular Therapy

Jiří Neužil is Head of the Laboratory of Molecular Therapy. It focuses its activities, similarly to its sister Australian group (Mitochondria, Apoptosis and Cancer Research Group, Griffith University, Southport, Qld, Australia), on the design and development of new anticancer agents, particularly vitamin E analogues that are effective and selective for malignant cells. In particular, there is scientific interest in the molecular mechanisms of apoptosis induced by such agents, including mitochondrial destabilization pathways. So-called mitokans, low molecular weight substances exhibiting anti-cancer activity through mitochondria, have been defined and characterized. These substances are particularly noteworthy from a translational perspective since it is now clear that tumors are highly heterogeneous in terms of mutations, even in different regions of the same tumor.

The laboratory investigates mainly mitokans from the group of vitamin E analogues, represented by redox inactive α-tocopheryl succinate (α-TOS). It exhibits high apoptogenic activity in many cancer cell lines while being non-toxic to normal cells. This in vitro proapoptotic activity is analogous to in vivo anti-cancer activity in  murine tumor models, as demonstrated for rectal, breast and mesothelioma tumors. With this finding, α-TOS is of considerable translational importance and becomes a starting point for the development of more effective agents.

In an effort to characterize pathways regulating the transmission of apoptotic signals in cancer cells triggered by α-TOS, Neuzil et al. a new target for anticancer drugs, mitochondrial complex II (CII). They found that α-TOS and similar agents interact with the proximal and distal ubiquinone CII binding site (UbQ), thereby replacing UbQ in CII. CII, by virtue of its succinate dehydrogenase (SDH) activity, converts the succinate to fumarate as a component of the tricarboxylic acid cycle (TCA). The electrons released by this reaction are normally taken over by UbQ and transferred to the CIII electron transport chain (ETC), part of oxidative phosphorylation. When UbQ is replaced by α-TOS or similar substances, electrons react with molecular oxygen and cause superoxide formation, triggering an apoptotic signaling cascade.

In an effort to increase the apoptogenic activity of α-TOS, the substance has been modified by attaching a cationic triphenylphosphonium (TPP) moiety that causes the accumulation of an agent (mitochondrially targeted vitamin E succinate, MitoVES) between the mitochondrial inner membrane and the mitochondrial matrix. This increases the apoptogenic activity of the parent compound by 1-2 orders of magnitude. Importantly, this increase in cancer cell toxicity will not affect the selectivity of the substance for malignant cells. The laboratory’s approach to cancer therapy by hanging lipophilic cations (such as TPP) to anti-cancer agents represents a new paradigm for effective cancer treatment. The group continues on this line of research to synthesize new, more potent mitochondria-targeted anti-cancer agents. In particular, they plan to initiate translational research to translate their new drugs into clinical practice.

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